Immunity, Inflammation and Disease最新文献_第2页

Genetic Variants of the IL-23/IL-17 Axis and Its Association With Periodontal Disease: A Systematic Review

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-31 DOI: 10.1002/iid3.70147

Ruth Rodríguez-Montaño, Mario Alberto Alarcón-Sánchez, Sarah Monserrat Lomelí-Martínez, Cristina Hermila Martínez-Bugarin, Artak Heboyan

Background

The objective of this systematic review was to identify genetic variants of the IL-23, IL-17, IL-23R and IL-17R genes and isoforms and its possible association with increased development of periodontitis and peri-implantitis.

Methods

A systematic review was prepared according to the guidelines, registered in the OSF database with the registration number: 10.17605/OSF. IO/X95ZC. The electronic search was performed in four databases: PubMed, Scopus, Web of Science, and Google Scholar from 1984 until March 15th, 2024. The JBI Critical Appraisal Checklist for Case-Control Studies was used to assess the quality of included studies.

Results

Eighteen papers with a case-control design were those that ultimately met the eligibility criteria. A total of 3904 individuals (2315 with periodontitis and 90 with peri-implantitis), and 1589 healthy subjects) were studied. The age range of the study population was 14–70 years, with a mean age ± (SD) of 40.43 ± 6.33 years. A total of 28 genetic variants corresponding to the IL-17A (rs 2275913, rs 3819024, rs 10484879) IL-17F (rs 763780), IL-17R (rs 879576) and IL-23R (rs 11209026) genes were analyzed in this study. Six (33.3%) studies found an association between the IL-17A 197 G/A (rs 2275913) genetic variant and peri-implantitis and periodontitis. One study (5.5%) found an association between the IL-17A rs10484879 variant and peri-implantitis and periodontitis.

Conclusion

Six polymorphisms were evaluated, highlighting rs 2275913 of the cytokine IL-17A in patients with periodontitis or peri-implantitis. Only 50% of studies found an association despite having a small sample. This suggests that other factors such as the degree of disease, systemic diseases and ethnic groups studied may play a role.

{"title":"Genetic Variants of the IL-23/IL-17 Axis and Its Association With Periodontal Disease: A Systematic Review","authors":"Ruth Rodríguez-Montaño, Mario Alberto Alarcón-Sánchez, Sarah Monserrat Lomelí-Martínez, Cristina Hermila Martínez-Bugarin, Artak Heboyan","doi":"10.1002/iid3.70147","DOIUrl":"10.1002/iid3.70147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this systematic review was to identify genetic variants of the <i>IL-23</i>, <i>IL-17</i>, <i>IL-23R</i> and <i>IL-17R</i> genes and isoforms and its possible association with increased development of periodontitis and peri-implantitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was prepared according to the guidelines, registered in the OSF database with the registration number: 10.17605/OSF. IO/X95ZC. The electronic search was performed in four databases: PubMed, Scopus, Web of Science, and Google Scholar from 1984 until March 15th, 2024. The JBI Critical Appraisal Checklist for Case-Control Studies was used to assess the quality of included studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighteen papers with a case-control design were those that ultimately met the eligibility criteria. A total of 3904 individuals (2315 with periodontitis and 90 with peri-implantitis), and 1589 healthy subjects) were studied. The age range of the study population was 14–70 years, with a mean age ± (SD) of 40.43 ± 6.33 years. A total of 28 genetic variants corresponding to the <i>IL-17A</i> (rs 2275913, rs 3819024, rs 10484879) <i>IL-17F</i> (rs 763780), <i>IL-17R</i> (rs 879576) and <i>IL-23R</i> (rs 11209026) genes were analyzed in this study. Six (33.3%) studies found an association between the <i>IL-17A</i> 197 G/A (rs 2275913) genetic variant and peri-implantitis and periodontitis. One study (5.5%) found an association between the <i>IL-17A</i> rs10484879 variant and peri-implantitis and periodontitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Six polymorphisms were evaluated, highlighting rs 2275913 of the cytokine IL-17A in patients with periodontitis or peri-implantitis. Only 50% of studies found an association despite having a small sample. This suggests that other factors such as the degree of disease, systemic diseases and ethnic groups studied may play a role.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C9orf72 Alleviates DSS‑Induced Ulcerative Colitis via the cGAS-STING Pathway

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-28 DOI: 10.1002/iid3.70139

Yue Wang, Ting Xu, Wenjun Wang

Purpose

C9orf72 deficiency contributes to severe inflammation in mice. Ulcerative colitis (UC) is a chronic inflammatory disorder with the shortage of clinical success. However, whether C9orf72 is involved in the progression of UC is not fully understood. This study investigated whether C9orf72 could alleviate dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced colitis in Caco-2 cells.

Methods

Mice were injected AAV9-C9orf72 lentivirus through tail vein and fed 3% DSS for a week. Caco-2 cells were cultured to establish C9orf723 overexpressed model. Histopathological examination, level of inflammation, cGAS-STING pathway, and gut barrier function were detected in mice and cells.

Results

C9orf72 overexpression in mice attenuated DSS-induced colitis and intestinal epithelial barrier damage by stimulating ZO-1 and Occludin expression. In LPS-induced Caco-2 cells, C9orf72 overexpression increased cell viability and the expression of ZO-1 and Occludin. C9orf72 overexpression alleviated inflammation by inhibiting the cGAS-STING pathway in colonic tissue and Caco-2 cells.

Conclusion

C9orf72 overexpression attenuated DSS-induced colitis and intestinal epithelial barrier damage by inhibiting the cGAS-STING pathway. C9orf72 may present a target for mitigating UC.

{"title":"C9orf72 Alleviates DSS‑Induced Ulcerative Colitis via the cGAS-STING Pathway","authors":"Yue Wang, Ting Xu, Wenjun Wang","doi":"10.1002/iid3.70139","DOIUrl":"10.1002/iid3.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>C9orf72 deficiency contributes to severe inflammation in mice. Ulcerative colitis (UC) is a chronic inflammatory disorder with the shortage of clinical success. However, whether C9orf72 is involved in the progression of UC is not fully understood. This study investigated whether C9orf72 could alleviate dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced colitis in Caco-2 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were injected AAV9-C9orf72 lentivirus through tail vein and fed 3% DSS for a week. Caco-2 cells were cultured to establish C9orf723 overexpressed model. Histopathological examination, level of inflammation, cGAS-STING pathway, and gut barrier function were detected in mice and cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>C9orf72 overexpression in mice attenuated DSS-induced colitis and intestinal epithelial barrier damage by stimulating ZO-1 and Occludin expression. In LPS-induced Caco-2 cells, C9orf72 overexpression increased cell viability and the expression of ZO-1 and Occludin. C9orf72 overexpression alleviated inflammation by inhibiting the cGAS-STING pathway in colonic tissue and Caco-2 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>C9orf72 overexpression attenuated DSS-induced colitis and intestinal epithelial barrier damage by inhibiting the cGAS-STING pathway. C9orf72 may present a target for mitigating UC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Changes in Serum Immunoglobulin Levels Play as Predictors of Treatment Response and Prognosis in Pediatric Idiopathic Nephrotic Syndrome During the Remission Phase

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-27 DOI: 10.1002/iid3.70144

Amin sadat Sharif, Naghmeh Nickravesh, Marzieh Heidarzadeh Arani, Mohammad Javad Azadchehr, Hossein Motedayyen

Background

Nephrotic syndrome is an immune-mediated renal disorder characterized by T-cell and B-cell dysfunctions with changes in immunoglobulin (Ig) levels and the IgG:IgM ratio. Therefore, this study aimed to determine whether the serum level of Igs can be considered as an index to predict the response to treatment and the prognosis of idiopathic nephrotic syndrome (INS) in children in the remission phase.

Methods

The study population consisted of 38 children with INS in the remission phase and 38 age- and sex-matched healthy children. Blood samples were collected from participants and serum values of IgG, IgM, IgE, and IgA were measured using EISA KITS from Aptech Services. The IgG:IgM ratio was studied in the participants.

Results

Patients significantly increased IgM and IgE levels compared with healthy subjects, unlike IgG and IgA values (p < 0.001–0.05). Patients with steroid-resistant nephrotic syndrome (SRNS) had a significant increase in IgM levels compared with those with steroid-sensitive nephrotic syndrome (SSNS) (p < 0.05). While, subjects with SRNS showed significant reductions in IgG and IgA values (p < 0.01). There were significant differences in the levels of IgG and IgM between steroid-sensitive patients with and without a history of relapse (p < 0.01). Furthermore, patients with steroid-independent and frequently relapsing NS showed a significant increase in IgE value compared with that of subjects with steroid-dependent and relapse (p < 0.05). The ratio of IgG/IgM was significantly reduced in patients compared with healthy individuals (p < 0.05). Other results indicated that there was a significant difference between patients with steroid-independent and steroid-dependent who had a history of relapse (p < 0.01).

Conclusion

Alterations in serum Ig values can be considered as predictors of treatment response and prognosis in pediatric idiopathic nephrotic syndrome during the remission phase.

{"title":"Changes in Serum Immunoglobulin Levels Play as Predictors of Treatment Response and Prognosis in Pediatric Idiopathic Nephrotic Syndrome During the Remission Phase","authors":"Amin sadat Sharif, Naghmeh Nickravesh, Marzieh Heidarzadeh Arani, Mohammad Javad Azadchehr, Hossein Motedayyen","doi":"10.1002/iid3.70144","DOIUrl":"10.1002/iid3.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nephrotic syndrome is an immune-mediated renal disorder characterized by T-cell and B-cell dysfunctions with changes in immunoglobulin (Ig) levels and the IgG:IgM ratio. Therefore, this study aimed to determine whether the serum level of Igs can be considered as an index to predict the response to treatment and the prognosis of idiopathic nephrotic syndrome (INS) in children in the remission phase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study population consisted of 38 children with INS in the remission phase and 38 age- and sex-matched healthy children. Blood samples were collected from participants and serum values of IgG, IgM, IgE, and IgA were measured using EISA KITS from Aptech Services. The IgG:IgM ratio was studied in the participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients significantly increased IgM and IgE levels compared with healthy subjects, unlike IgG and IgA values (<i>p</i> < 0.001–0.05). Patients with steroid-resistant nephrotic syndrome (SRNS) had a significant increase in IgM levels compared with those with steroid-sensitive nephrotic syndrome (SSNS) (<i>p</i> < 0.05). While, subjects with SRNS showed significant reductions in IgG and IgA values (<i>p</i> < 0.01). There were significant differences in the levels of IgG and IgM between steroid-sensitive patients with and without a history of relapse (<i>p</i> < 0.01). Furthermore, patients with steroid-independent and frequently relapsing NS showed a significant increase in IgE value compared with that of subjects with steroid-dependent and relapse (<i>p</i> < 0.05). The ratio of IgG/IgM was significantly reduced in patients compared with healthy individuals (<i>p</i> < 0.05). Other results indicated that there was a significant difference between patients with steroid-independent and steroid-dependent who had a history of relapse (<i>p</i> < 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Alterations in serum Ig values can be considered as predictors of treatment response and prognosis in pediatric idiopathic nephrotic syndrome during the remission phase.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Characteristics During and After COVID-19 Infection Among Healthcare Workers During the First Wave of Omicron in Chongqing, China

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-27 DOI: 10.1002/iid3.70141

Haoling Tang, Zhiwei Chen, Tianquan Huang, Pingping Yu, Qiao Tang, Yue Qiu, Yunling Xue, Jing Tang, Nan Cai, Hong Ren, Mingli Peng, Peng Hu

Background

Revealing the clinical manifestations and associations of COVID-19 before and after negative transition remains an area of significant uncertainty. The aim of this study is to investigate the clinical characteristics observed during and after Omicron infection among a specific population, namely healthcare workers (HCWs).

Methods

From November 4, 2022, to January 15, 2023, HCWs in our hospital were enrolled to document clinical symptoms, prevention, and treatment for COVID-19 using a structured questionnaire.

Results

A total of 1101 HCWs were included, with SARS-CoV-2 infection detected in 78.20% (861/1101) during the observation period. The median duration for nucleic acid conversion was 8 days. Forty-three symptoms were identified during SARS-CoV-2 infection (11 symptoms per individual). The common symptoms were fever, cough, headache, phlegm production, and fatigue (60.67%–83.29%). These symptoms can be further categorized into five groups: fever type, upper respiratory tract type, influenza type, digestive system type, and systemic type—all showing complex and diverse patterns. Following SARS-CoV-2 infection, a total of 19 symptoms were recorded including four newly emerged ones: reduced lung capacity, memory loss, lethargy, and inattention. Importantly, we observed a significant association between gastrointestinal symptoms during the nucleic acid positive phase and subsequent neuropsychiatric manifestations after negative conversion. Interestingly, females experiencing menstruation or pregnancy exhibited a higher risk of infection, while inhaled vaccines and thymosin demonstrated a protective effect against SARS-CoV-2 infection.

Conclusions

The clinical manifestations observed in HCWs during and after Omicron infection displayed intricate patterns, shedding new light on the complex interplay between SARS-CoV-2 and humans.

{"title":"Clinical Characteristics During and After COVID-19 Infection Among Healthcare Workers During the First Wave of Omicron in Chongqing, China","authors":"Haoling Tang, Zhiwei Chen, Tianquan Huang, Pingping Yu, Qiao Tang, Yue Qiu, Yunling Xue, Jing Tang, Nan Cai, Hong Ren, Mingli Peng, Peng Hu","doi":"10.1002/iid3.70141","DOIUrl":"10.1002/iid3.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Revealing the clinical manifestations and associations of COVID-19 before and after negative transition remains an area of significant uncertainty. The aim of this study is to investigate the clinical characteristics observed during and after Omicron infection among a specific population, namely healthcare workers (HCWs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From November 4, 2022, to January 15, 2023, HCWs in our hospital were enrolled to document clinical symptoms, prevention, and treatment for COVID-19 using a structured questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1101 HCWs were included, with SARS-CoV-2 infection detected in 78.20% (861/1101) during the observation period. The median duration for nucleic acid conversion was 8 days. Forty-three symptoms were identified during SARS-CoV-2 infection (11 symptoms per individual). The common symptoms were fever, cough, headache, phlegm production, and fatigue (60.67%–83.29%). These symptoms can be further categorized into five groups: fever type, upper respiratory tract type, influenza type, digestive system type, and systemic type—all showing complex and diverse patterns. Following SARS-CoV-2 infection, a total of 19 symptoms were recorded including four newly emerged ones: reduced lung capacity, memory loss, lethargy, and inattention. Importantly, we observed a significant association between gastrointestinal symptoms during the nucleic acid positive phase and subsequent neuropsychiatric manifestations after negative conversion. Interestingly, females experiencing menstruation or pregnancy exhibited a higher risk of infection, while inhaled vaccines and thymosin demonstrated a protective effect against SARS-CoV-2 infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The clinical manifestations observed in HCWs during and after Omicron infection displayed intricate patterns, shedding new light on the complex interplay between SARS-CoV-2 and humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blast-Overpressure Induced Modulation of PARP-SIRT-NRF2 Axis in Stress Signaling of Astrocytes and Microglia

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-27 DOI: 10.1002/iid3.70106

Vijaya Prakash Krishnan Muthaiah, Kathiravan Kaliyappan, Ramkumar Thiayagarajan, Supriya Mahajan, Krishnamoorthy Gunasekaran

Background

The pathomechanism of blast traumatic brain injury (TBI) and blunt TBI is different. In blast injury, evidence indicates that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive, and treatments have been symptomatic. Poly adenosine diphosphate (ADP) ribose polymerase-1 (PARP1) is implicated in the parthanatos and secondary neuroinflammation. Animal studies indicate the over-activation of PARP1 as a significant downstream event underlying the neurological sequelae of several traumatic and neurodegenerative disorders, irrespective of the mode of cell death. PARP over-activation forms ADP polymers on several nuclear proteins, known as trans-PARylation, by consuming nicotinamide adenine dinucleotide (NAD⁺) and ATP. As NAD⁺ is a substrate for sirtuins, ithas also been implicated in the oxidative stress underlying TBI pathology.

Hypothesis

We recently established the implication of PARP1 following blast overpressure (BOP) and its differential response on astrocytes and microglial cells. We found that the inhibition of PARP is proven beneficial by attenuating oxidative stress. In this study, we hypothesized the involvement of the PARP1-SIRT-NRF2 axis following induced blast-induced PARP over-activation in glial cells for the manifestation of oxidative stress in BOP insults.

Objective

The objective is to determine the downstream modulation of the PARP-SIRT-NRF2 axis and changes in ATP levels following blast exposure in astrocytes and microglia cell lines.

Results

As a result of NAD⁺ being a common substrate for PARP1 and Sirtuins, we found the decreased expression of SIRT1, SIRT3, and NRF2, a central transcriptional regulator for the expression of antioxidant genes. We found that ATP levels were elevated post-BOP from both glycolysis and oxidative phosphorylation (OXPHOS), an increase of ATP by glycolysis more significant than OXPHOS source, indicating the proinflammation post-BOP.

Conclusion

This result shows that blast-induced PARP1 over-activation impacts the deacetylation activity of sirtuins and consequently impacts the regulation of antioxidant levels in astrocytes and microglia.

{"title":"Blast-Overpressure Induced Modulation of PARP-SIRT-NRF2 Axis in Stress Signaling of Astrocytes and Microglia","authors":"Vijaya Prakash Krishnan Muthaiah, Kathiravan Kaliyappan, Ramkumar Thiayagarajan, Supriya Mahajan, Krishnamoorthy Gunasekaran","doi":"10.1002/iid3.70106","DOIUrl":"10.1002/iid3.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathomechanism of blast traumatic brain injury (TBI) and blunt TBI is different. In blast injury, evidence indicates that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive, and treatments have been symptomatic. Poly adenosine diphosphate (ADP) ribose polymerase-1 (PARP1) is implicated in the parthanatos and secondary neuroinflammation. Animal studies indicate the over-activation of PARP1 as a significant downstream event underlying the neurological sequelae of several traumatic and neurodegenerative disorders, irrespective of the mode of cell death. PARP over-activation forms ADP polymers on several nuclear proteins, known as trans-PARylation, by consuming nicotinamide adenine dinucleotide (NAD<sup>+</sup>) and ATP. As NAD<sup>+</sup> is a substrate for sirtuins, ithas also been implicated in the oxidative stress underlying TBI pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis</h3>\u0000 \u0000 <p>We recently established the implication of PARP1 following blast overpressure (BOP) and its differential response on astrocytes and microglial cells. We found that the inhibition of PARP is proven beneficial by attenuating oxidative stress. In this study, we hypothesized the involvement of the PARP1-SIRT-NRF2 axis following induced blast-induced PARP over-activation in glial cells for the manifestation of oxidative stress in BOP insults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective is to determine the downstream modulation of the PARP-SIRT-NRF2 axis and changes in ATP levels following blast exposure in astrocytes and microglia cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As a result of NAD<sup>+</sup> being a common substrate for PARP1 and Sirtuins, we found the decreased expression of SIRT1, SIRT3, and NRF2, a central transcriptional regulator for the expression of antioxidant genes. We found that ATP levels were elevated post-BOP from both glycolysis and oxidative phosphorylation (OXPHOS), an increase of ATP by glycolysis more significant than OXPHOS source, indicating the proinflammation post-BOP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This result shows that blast-induced PARP1 over-activation impacts the deacetylation activity of sirtuins and consequently impacts the regulation of antioxidant levels in astrocytes and microglia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systemic Lupus Erythematosus Presenting as Anorexia Nervosa in a Middle-Aged Woman: A Rare Case Report and Literature Review

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-27 DOI: 10.1002/iid3.70083

Maen Nizam Baroudi, Anwar I. Joudeh, Mohammed Kays Alattiya, Abdo Qaid Ahmed Lutf, Hassan Abuzaid, Salah Mahdi

Background

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystemic involvement and unclear etiology. Although SLE could be linked to multiple neuropsychiatric manifestations, the co-occurrence of anorexia nervosa was only described through a few case reports that mainly affected children and adolescents.

Case Presentation

a 40-year-old Filipina woman presented to hospital with a 3-day history of agitation, anorexia and auditory hallucinations. She also had restrictive dietary habits with substantial weight loss and excessive fear of weight gain for the past several months. Her medical history was also noticeable for a 3-month history of erythematous non-itchy skin rash. On examination, the patient was pale and underweight. She had angular stomatitis, bilateral exophthalmos, and diffuse goiter. Skin examination revealed diffuse scaly and erythematous rash over the neck and upper torso with post-inflammatory skin discoloration. Laboratory investigations showed pancytopenia, high serum creatinine, and +1 proteinuria. Further workup confirmed thyrotoxicosis due to Graves disease as well as having multiple positive autoantibodies including antinuclear antibody (ANA) which were suggestive for SLE. A subsequent kidney biopsy demonstrated class IV diffuse lupus nephritis. The patient was treated successfully with intravenous pulse steroid therapy, rituximab, and antithyroid medications with no residual symptoms or laboratory abnormalities.

Conclusions

The concurrence of anorexia nervosa with SLE and the complete resolution of anorexia nervosa symptoms with immunosuppressive therapy suggest common autoinflammatory pathogenesis for both conditions. Further research is needed to elucidate any potential association between SLE and anorexia nervosa.

{"title":"Systemic Lupus Erythematosus Presenting as Anorexia Nervosa in a Middle-Aged Woman: A Rare Case Report and Literature Review","authors":"Maen Nizam Baroudi, Anwar I. Joudeh, Mohammed Kays Alattiya, Abdo Qaid Ahmed Lutf, Hassan Abuzaid, Salah Mahdi","doi":"10.1002/iid3.70083","DOIUrl":"10.1002/iid3.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystemic involvement and unclear etiology. Although SLE could be linked to multiple neuropsychiatric manifestations, the co-occurrence of anorexia nervosa was only described through a few case reports that mainly affected children and adolescents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>a 40-year-old Filipina woman presented to hospital with a 3-day history of agitation, anorexia and auditory hallucinations. She also had restrictive dietary habits with substantial weight loss and excessive fear of weight gain for the past several months. Her medical history was also noticeable for a 3-month history of erythematous non-itchy skin rash. On examination, the patient was pale and underweight. She had angular stomatitis, bilateral exophthalmos, and diffuse goiter. Skin examination revealed diffuse scaly and erythematous rash over the neck and upper torso with post-inflammatory skin discoloration. Laboratory investigations showed pancytopenia, high serum creatinine, and +1 proteinuria. Further workup confirmed thyrotoxicosis due to Graves disease as well as having multiple positive autoantibodies including antinuclear antibody (ANA) which were suggestive for SLE. A subsequent kidney biopsy demonstrated class IV diffuse lupus nephritis. The patient was treated successfully with intravenous pulse steroid therapy, rituximab, and antithyroid medications with no residual symptoms or laboratory abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The concurrence of anorexia nervosa with SLE and the complete resolution of anorexia nervosa symptoms with immunosuppressive therapy suggest common autoinflammatory pathogenesis for both conditions. Further research is needed to elucidate any potential association between SLE and anorexia nervosa.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allergic Rhinitis and Its Associated Co-Morbidities Among Patients Attending the ENT Department at Kilimanjaro Christian Medical Center in Northern Tanzania: Cross-Sectional Study

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-24 DOI: 10.1002/iid3.70130

Kenneth Mlay, Gasper Temba, Adrian Matasha, Pendael Mzonge, Denis Katundu, Desderius Chussi

Introduction

Allergic rhinitis is the specific inflammation against allergen by immune defense cells on the nasal mucosa, which can lead to chronic nasal symptoms such as sneezing, itching, runny nose, and nasal congestion. It is associated with high morbidity including sinusitis, asthma, otitis media, hypertrophied inferior turbinate, and nasal polyps. Despite its complications, it remains poorly recognized and tracked.

Methods

A cross-sectional hospital-based study was done, a total of 221 patients received Ear, Nose And Throat services at Kilimanjaro Christian Medical Center during the study period all patients with a clinical diagnosis of allergic rhinitis were captured; Data was collected using a pre-tested coded questionnaire (Score For Allergic Rhinitis). The data was then analyzed using SPSS version 22.

Results

A total of 221 patients with a clinical diagnosis of allergic rhinitis were approached in a 6 months study period, 111 (50.2%) were females, and 140 (63.4%) were residing in urban areas. The prevalence of allergic rhinitis was 23.9%. Factors such as age OR 0.12, 95% CI (0.03; 0.40), education OR 0.13, 95% CI (0.04; 0.44), occupation OR 3.75, 95% CI (1.36; 10.32), adenotonsillar hypertrophy OR 4.66, 95% CI (2.21; 9.80), and OME OR 4.11, 95% CI (1.32; 12.83) (p = 0.009) were found to be significantly associated with allergic rhinitis. 60.4%, Inferior turbinate hypertrophy is the leading co-morbidity of allergic rhinitis which accounts for 64.7%.

Conclusion

Allergic rhinitis is among the common health problems affecting Tanzanians. It is a commonly seen disorder in younger age ( < 15 years) which is in correlation with other studies done in Africa and worldwide.

{"title":"Allergic Rhinitis and Its Associated Co-Morbidities Among Patients Attending the ENT Department at Kilimanjaro Christian Medical Center in Northern Tanzania: Cross-Sectional Study","authors":"Kenneth Mlay, Gasper Temba, Adrian Matasha, Pendael Mzonge, Denis Katundu, Desderius Chussi","doi":"10.1002/iid3.70130","DOIUrl":"10.1002/iid3.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Allergic rhinitis is the specific inflammation against allergen by immune defense cells on the nasal mucosa, which can lead to chronic nasal symptoms such as sneezing, itching, runny nose, and nasal congestion. It is associated with high morbidity including sinusitis, asthma, otitis media, hypertrophied inferior turbinate, and nasal polyps. Despite its complications, it remains poorly recognized and tracked.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional hospital-based study was done, a total of 221 patients received Ear, Nose And Throat services at Kilimanjaro Christian Medical Center during the study period all patients with a clinical diagnosis of allergic rhinitis were captured; Data was collected using a pre-tested coded questionnaire (Score For Allergic Rhinitis). The data was then analyzed using SPSS version 22.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 221 patients with a clinical diagnosis of allergic rhinitis were approached in a 6 months study period, 111 (50.2%) were females, and 140 (63.4%) were residing in urban areas. The prevalence of allergic rhinitis was 23.9%. Factors such as age OR 0.12, 95% CI (0.03; 0.40), education OR 0.13, 95% CI (0.04; 0.44), occupation OR 3.75, 95% CI (1.36; 10.32), adenotonsillar hypertrophy OR 4.66, 95% CI (2.21; 9.80), and OME OR 4.11, 95% CI (1.32; 12.83) (<i>p</i> = 0.009) were found to be significantly associated with allergic rhinitis. 60.4%, Inferior turbinate hypertrophy is the leading co-morbidity of allergic rhinitis which accounts for 64.7%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Allergic rhinitis is among the common health problems affecting Tanzanians. It is a commonly seen disorder in younger age ( < 15 years) which is in correlation with other studies done in Africa and worldwide.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification and Functional Analysis of PANoptosis-Associated Genes in the Progression From Sepsis to ARDS

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-24 DOI: 10.1002/iid3.70136

Zhong-Hua Lu, Yan Tang, Hu Chen, Feng Liu, Mei Liu, Lu Fu, Xian-Kai Wang, Ming-Juan Li, Wei-Li Yu, Yun Sun

Background

Sepsis and acute respiratory distress syndrome (ARDS) are common inflammatory conditions in intensive care, with ARDS significantly increasing mortality in septic patients. PANoptosis, a newly discovered form of programmed cell death involving multiple cell death pathways, plays a critical role in inflammatory diseases. This study aims to elucidate the PANoptosis-related genes (PRGs) and their involvement in the progression of sepsis to ARDS.

Methods

This study analyzed differentially expressed genes (DEGs) associated with PRGs to explore their role in the progression of immune disorders from sepsis to septic ARDS. A diagnostic prediction model was constructed based on key PRGs identified through bioinformatics analysis. Functional enrichment analyses were conducted to determine pathway involvement, and correlations with immune cells were assessed. Mendelian randomization analysis was applied to investigate potential causal links between specific PRGs and ARDS. Immunohistochemical analysis was used to evaluate PRG expression in lung tissue.

Results

The prediction model effectively distinguished septic ARDS patients from those with sepsis. NDRG1 expression was elevated in ARDS, while DDX3X, PTPRC, and TNFSF8 were downregulated. NDRG1 showed a positive correlation with activated dendritic cells, whereas DDX3X, PTPRC, and TNFSF8 were positively associated with neutrophils and negatively correlated with CD56bright NK cells. Functional enrichment analysis highlighted spliceosome function, MAPK signaling, endocytosis, and antigen processing pathways as significantly associated with these PRGs. Mendelian randomization suggested a causal link between NDRG1 and ARDS, and immunohistochemical analysis revealed its predominant expression near vascular walls. In a mouse model of sepsis, suppression of NDRG1 alleviated lung injury.

Conclusion

PANoptosis may contribute to immune dysregulation in sepsis-associated ARDS. NDRG1 is identified as a potential therapeutic target, offering new avenues for mitigating ARDS progression and improving patient outcomes.

{"title":"Identification and Functional Analysis of PANoptosis-Associated Genes in the Progression From Sepsis to ARDS","authors":"Zhong-Hua Lu, Yan Tang, Hu Chen, Feng Liu, Mei Liu, Lu Fu, Xian-Kai Wang, Ming-Juan Li, Wei-Li Yu, Yun Sun","doi":"10.1002/iid3.70136","DOIUrl":"10.1002/iid3.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis and acute respiratory distress syndrome (ARDS) are common inflammatory conditions in intensive care, with ARDS significantly increasing mortality in septic patients. PANoptosis, a newly discovered form of programmed cell death involving multiple cell death pathways, plays a critical role in inflammatory diseases. This study aims to elucidate the PANoptosis-related genes (PRGs) and their involvement in the progression of sepsis to ARDS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study analyzed differentially expressed genes (DEGs) associated with PRGs to explore their role in the progression of immune disorders from sepsis to septic ARDS. A diagnostic prediction model was constructed based on key PRGs identified through bioinformatics analysis. Functional enrichment analyses were conducted to determine pathway involvement, and correlations with immune cells were assessed. Mendelian randomization analysis was applied to investigate potential causal links between specific PRGs and ARDS. Immunohistochemical analysis was used to evaluate PRG expression in lung tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prediction model effectively distinguished septic ARDS patients from those with sepsis. NDRG1 expression was elevated in ARDS, while DDX3X, PTPRC, and TNFSF8 were downregulated. NDRG1 showed a positive correlation with activated dendritic cells, whereas DDX3X, PTPRC, and TNFSF8 were positively associated with neutrophils and negatively correlated with CD56bright NK cells. Functional enrichment analysis highlighted spliceosome function, MAPK signaling, endocytosis, and antigen processing pathways as significantly associated with these PRGs. Mendelian randomization suggested a causal link between NDRG1 and ARDS, and immunohistochemical analysis revealed its predominant expression near vascular walls. In a mouse model of sepsis, suppression of NDRG1 alleviated lung injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PANoptosis may contribute to immune dysregulation in sepsis-associated ARDS. NDRG1 is identified as a potential therapeutic target, offering new avenues for mitigating ARDS progression and improving patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential Biomarkers for Predicting the Risk of Developing Into Long COVID After COVID-19 Infection

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-24 DOI: 10.1002/iid3.70137

Zhiyong Hou, Yu Ming, Jun Liu, Zhong Wang

Background

Long COVID, a heterogeneous condition characterized by a range of physical and neuropsychiatric presentations, can be presented with a proportion of COVID-19-infected individuals.

Methods

Transcriptomic data sets of those within gene expression profiles of COVID-19, long COVID, and healthy controls were retrieved from the GEO database. Differentially expressed genes (DEGs) falling under COVID-19 and long COVID were identified with R packages, and contemporaneously conducted module detection was performed with the Modular Pharmacology Platform (http://112.86.129.72:48081/). The integration of both DEGs and differentially expressed module-genes (DEMGs) regarding long COVID and COVID-19 was intersected by following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).

Results

There were 11 and 62 differentially expressed modules, 1837 and 179 DEGs, as well as 103 and 508 DEMGs acquiring identified for both COVID-19 and long COVID, notably enriched in the immune-correlated signaling pathways. The immune infiltrating cells of long COVID and COVID-19 were comparatively and respectively assessed via CIBERSORT, ssGSEA, and xCell algorithms. Subsequently, the screening of hub genes involved employing the SVM-RFE, RF, XGBoost algorithms, and logistic regression analysis. Among the 67 candidate genes were processed with machine learning algorithms and logistic regression, a subgroup consisting of CEP55, CDCA2, MELK, and DEPDC1B, was at last identified as potential biomarkers for predicting the risk of the progression into long COVID after COVID-19 infections. The predicting performance of the potential biomarkers was quantified with a ROC value of 0.8762542, which proved the combination of potential biomarkers provided the highest performance.

Conclusions

In summary, we identified a subgroup of potential biomarkers for predicting the risk of the progression into long COVID after COVID-19 infection, which could be partly elucidation of the associated molecular mechanisms for long COVID.

{"title":"Potential Biomarkers for Predicting the Risk of Developing Into Long COVID After COVID-19 Infection","authors":"Zhiyong Hou, Yu Ming, Jun Liu, Zhong Wang","doi":"10.1002/iid3.70137","DOIUrl":"10.1002/iid3.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Long COVID, a heterogeneous condition characterized by a range of physical and neuropsychiatric presentations, can be presented with a proportion of COVID-19-infected individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transcriptomic data sets of those within gene expression profiles of COVID-19, long COVID, and healthy controls were retrieved from the GEO database. Differentially expressed genes (DEGs) falling under COVID-19 and long COVID were identified with R packages, and contemporaneously conducted module detection was performed with the Modular Pharmacology Platform (http://112.86.129.72:48081/). The integration of both DEGs and differentially expressed module-genes (DEMGs) regarding long COVID and COVID-19 was intersected by following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 11 and 62 differentially expressed modules, 1837 and 179 DEGs, as well as 103 and 508 DEMGs acquiring identified for both COVID-19 and long COVID, notably enriched in the immune-correlated signaling pathways. The immune infiltrating cells of long COVID and COVID-19 were comparatively and respectively assessed via CIBERSORT, ssGSEA, and xCell algorithms. Subsequently, the screening of hub genes involved employing the SVM-RFE, RF, XGBoost algorithms, and logistic regression analysis. Among the 67 candidate genes were processed with machine learning algorithms and logistic regression, a subgroup consisting of CEP55, CDCA2, MELK, and DEPDC1B, was at last identified as potential biomarkers for predicting the risk of the progression into long COVID after COVID-19 infections. The predicting performance of the potential biomarkers was quantified with a ROC value of 0.8762542, which proved the combination of potential biomarkers provided the highest performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, we identified a subgroup of potential biomarkers for predicting the risk of the progression into long COVID after COVID-19 infection, which could be partly elucidation of the associated molecular mechanisms for long COVID.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2025-01-24 DOI: 10.1002/iid3.70133

Christine W. Wiger, Trine Ranheim, Henriette Arnesen, Jarle Vaage, Søren E. Pischke, Arne Yndestad, Kåre-Olav Stensløkken, May-Kristin Torp

Background

Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or Escherichia coli-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia–reperfusion.

Methods

Isolated C57BL/6N male mouse hearts were perfused for 120 min, with either LPS, E. coli, with and without CLI-095 (TLR4 inhibitor). Primary adult mouse cardiomyocytes were treated with LPS or LPS + CLI-095. Isolated hearts, exposed to 35 min of global ischemia, were treated with either vehicle or CLI-095 during reperfusion. Infarct size was quantified by triphenyltetrazolium staining. Cytokine expression was analyzed with ELISA, western blot analysis, and qPCR.

Results

In isolated hearts, E. coli increased the expression of proinflammatory cytokines (IL-6 and CXCL2), which was not attenuated with TLR4 inhibition. TLR4 inhibition reduced expression (p = 0.004) and release of IL-6 (p < 0.0001) in LPS-exposed isolated hearts. LPS activated the nuclear-factor κ-light-chain-enhancer of activated B cells signaling pathway (NF-κB) in primary adult cardiomyocytes. Moreover, TLR4 inhibition reduced LPS-induced mRNA expression and release of IL-6 in primary adult cardiomyocytes. Isolated hearts treated with CLI-095 during reperfusion after ischemia (induced DAMPs release) showed reduced infarct size (39 ± 17% to 26 ± 8%, p = 0.034) and decreased IL-6 release (p = 0.006).

Conclusion

Inhibition of TLR4 reduced proinflammatory signaling and cytokine release in LPS-treated and ischemia–reperfused isolated mouse hearts and in primary adult murine cardiomyocytes.

{"title":"TLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes","authors":"Christine W. Wiger, Trine Ranheim, Henriette Arnesen, Jarle Vaage, Søren E. Pischke, Arne Yndestad, Kåre-Olav Stensløkken, May-Kristin Torp","doi":"10.1002/iid3.70133","DOIUrl":"10.1002/iid3.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or <i>Escherichia coli</i>-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia–reperfusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Isolated C57BL/6N male mouse hearts were perfused for 120 min, with either LPS, <i>E. coli</i>, with and without CLI-095 (TLR4 inhibitor). Primary adult mouse cardiomyocytes were treated with LPS or LPS + CLI-095. Isolated hearts, exposed to 35 min of global ischemia, were treated with either vehicle or CLI-095 during reperfusion. Infarct size was quantified by triphenyltetrazolium staining. Cytokine expression was analyzed with ELISA, western blot analysis, and qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In isolated hearts, <i>E. coli</i> increased the expression of proinflammatory cytokines (IL-6 and CXCL2), which was not attenuated with TLR4 inhibition. TLR4 inhibition reduced expression (<i>p</i> = 0.004) and release of IL-6 (<i>p</i> < 0.0001) in LPS-exposed isolated hearts. LPS activated the nuclear-factor κ-light-chain-enhancer of activated B cells signaling pathway (NF-κB) in primary adult cardiomyocytes. Moreover, TLR4 inhibition reduced LPS-induced mRNA expression and release of IL-6 in primary adult cardiomyocytes. Isolated hearts treated with CLI-095 during reperfusion after ischemia (induced DAMPs release) showed reduced infarct size (39 ± 17% to 26 ± 8%, <i>p</i> = 0.034) and decreased IL-6 release (<i>p</i> = 0.006).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Inhibition of TLR4 reduced proinflammatory signaling and cytokine release in LPS-treated and ischemia–reperfused isolated mouse hearts and in primary adult murine cardiomyocytes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0