We aimed to understand the host and microbe interactions at the time of infection and inflammatory response in amoebic liver abscess (ALA) patients based on toll-like receptor (TLR) expression (mRNA), cytokine and IgG subtypes levels.
Methods and results
Liver aspirates from 100 ALA patients and 11 liver autopsy samples were used as negative controls. Blood samples from 100 ALA and 41 healthy individuals were collected. mRNA expression of TLR 1 to 9 genes was measured using reverse transcriptase polymerase chain reaction (RT-PCR). Serum cytokines level was quantified by flow cytometry. In-house ELISA for the analysis of IgG and its subtypes in the serum samples was performed. A total of 7 TLR genes (TLR1, TLR2, TLR4, TLR6, TLR7, TLR8 and TLR9) and 6 TLR genes (TLR1, TLR2, TLR3, TLR4, TLR5 and TLR8) were found to be elevated in liver aspirates and PBMCs respectively. Increased serum cytokine levels were observed in ALA patients vs. healthy controls. Interestingly, a significant increase in IgG and its subtypes (IgG1, IgG3 and IgG4) was found in the serum of ALA patients.
Conclusion
Increased levels of TLR, pro- and anti-inflammatory cytokines, IgG and its subtypes, are possibly linked with early-stage infection in ALA patients.
Impact statement
The role of TLRs in association with ALA might provide insights into new therapeutic strategies.
{"title":"Toll-like receptor upregulation in liver and peripheral blood mononuclear cells of patients with amoebic liver abscess","authors":"Sandhya Khunger , Abhishek Mewara , Upninder Kaur , Ajay Duseja , Pallab Ray , Naveen Kalra , Navneet Sharma , Rakesh Sehgal","doi":"10.1016/j.imbio.2025.152869","DOIUrl":"10.1016/j.imbio.2025.152869","url":null,"abstract":"<div><h3>Aim</h3><div>We aimed to understand the host and microbe interactions at the time of infection and inflammatory response in amoebic liver abscess (ALA) patients based on toll-like receptor (TLR) expression (mRNA), cytokine and IgG subtypes levels.</div></div><div><h3>Methods and results</h3><div>Liver aspirates from 100 ALA patients and 11 liver autopsy samples were used as negative controls. Blood samples from 100 ALA and 41 healthy individuals were collected. mRNA expression of TLR 1 to 9 genes was measured using reverse transcriptase polymerase chain reaction (RT-PCR). Serum cytokines level was quantified by flow cytometry. In-house ELISA for the analysis of IgG and its subtypes in the serum samples was performed. A total of 7 TLR genes (TLR1, TLR2, TLR4, TLR6, TLR7, TLR8 and TLR9) and 6 TLR genes (TLR1, TLR2, TLR3, TLR4, TLR5 and TLR8) were found to be elevated in liver aspirates and PBMCs respectively. Increased serum cytokine levels were observed in ALA patients vs. healthy controls. Interestingly, a significant increase in IgG and its subtypes (IgG1, IgG3 and IgG4) was found in the serum of ALA patients.</div></div><div><h3>Conclusion</h3><div>Increased levels of TLR, pro- and anti-inflammatory cytokines, IgG and its subtypes, are possibly linked with early-stage infection in ALA patients.</div></div><div><h3>Impact statement</h3><div>The role of TLRs in association with ALA might provide insights into new therapeutic strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152869"},"PeriodicalIF":2.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143303248","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}
COX inhibitors are frequently used for pain management during the perioperative period and may influence tumor progression and the tumor microenvironment by modulating inflammation and immune responses. This study investigates the effects of COX inhibitors on tumor growth and the immune microenvironment. In vivo experiments demonstrate that COX inhibitors can reduce tumor cell growth, elevate PD-L1 expression on tumor cells, and enhance the proportion of myeloid cells within the tumor immune microenvironment. Furthermore, COX inhibitors are found to improve the efficacy of the immune checkpoint inhibitor anti-PD-L1. These results underscore the influence of perioperative COX inhibitors on tumor immunity and suggest potential new strategies for optimizing tumor immunotherapy.
{"title":"Effect of perioperative analgesia on immunity in lung cancer","authors":"Xiaomin Fan , Ziqi Huang , Ziying Chen , Liang Yun , Xinjian Zhang","doi":"10.1016/j.imbio.2025.152867","DOIUrl":"10.1016/j.imbio.2025.152867","url":null,"abstract":"<div><div>COX inhibitors are frequently used for pain management during the perioperative period and may influence tumor progression and the tumor microenvironment by modulating inflammation and immune responses. This study investigates the effects of COX inhibitors on tumor growth and the immune microenvironment. In vivo experiments demonstrate that COX inhibitors can reduce tumor cell growth, elevate PD-L1 expression on tumor cells, and enhance the proportion of myeloid cells within the tumor immune microenvironment. Furthermore, COX inhibitors are found to improve the efficacy of the immune checkpoint inhibitor anti-PD-L1. These results underscore the influence of perioperative COX inhibitors on tumor immunity and suggest potential new strategies for optimizing tumor immunotherapy.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152867"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028665","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}
Pub Date : 2025-01-18DOI: 10.1016/j.imbio.2025.152870
Xue Luo , Xin Chen , Ying Gu , Honggang Jia , Xinyu Lin , Ling Wang , Jingyun Feng
Purpose
This study intends to investigate the relationship between FENDRR and miR-424-5p and their clinical significance in sepsis, aiming to provide new diagnostic markers and prognostic markers for sepsis.
Methods
136 patients with sepsis and 132 healthy volunteers were included as study subjects. The expression levels of FENDRR and miR-424-5p were detected by qPCR. ROC was applied to evaluate the diagnostic value of FENDRR and miR-424-5p. COX analyzed the independent risk factors for the occurrence of death in sepsis patients. Dual luciferase reporter assay detected the binding of FENDRR and miR-424-5p. The miR-424-5p target genes were predicted and enriched for GO function and KEGG pathway.
Results
FENDRR was up-regulated and miR-424-5p was down-regulated in patients with sepsis. FENDRR can target and bind to miR-424-5p. Both FENDRR and miR-424-5p showed significant diagnostic potential in sepsis and their combination significantly improved the diagnostic efficiency. FENDRR/miR-424-5p were significantly correlated with WBC, CRP, APACH II, and SOFA of sepsis patients. FENDRR and miR-424-5p were independent risk factors for mortality in sepsis patients. Sepsis patients with high FENDRR levels or low miR-424-5p levels had higher mortality. GO and KEGG enrichment analyses revealed that the targets of miR-424-5p were predominantly associated with cell functions and inflammatory signaling pathways.
Conclusion
Upregulated FENDRR and downregulated miR-424-5p expression can serve as biomarkers of sepsis with predictive value on the onset and prognostic outcome. FENDRR and miR-424-5p were correlated with the severity of sepsis and FENDRR can play a function in the sepsis progression via targeting miR-424-5p.
{"title":"LncRNA FENDRR/ miR-424-5p serves as a diagnostic biomarker for sepsis and its predictive value for clinical outcomes","authors":"Xue Luo , Xin Chen , Ying Gu , Honggang Jia , Xinyu Lin , Ling Wang , Jingyun Feng","doi":"10.1016/j.imbio.2025.152870","DOIUrl":"10.1016/j.imbio.2025.152870","url":null,"abstract":"<div><h3>Purpose</h3><div>This study intends to investigate the relationship between FENDRR and miR-424-5p and their clinical significance in sepsis, aiming to provide new diagnostic markers and prognostic markers for sepsis.</div></div><div><h3>Methods</h3><div>136 patients with sepsis and 132 healthy volunteers were included as study subjects. The expression levels of FENDRR and miR-424-5p were detected by qPCR. ROC was applied to evaluate the diagnostic value of FENDRR and miR-424-5p. COX analyzed the independent risk factors for the occurrence of death in sepsis patients. Dual luciferase reporter assay detected the binding of FENDRR and miR-424-5p. The miR-424-5p target genes were predicted and enriched for GO function and KEGG pathway.</div></div><div><h3>Results</h3><div>FENDRR was up-regulated and miR-424-5p was down-regulated in patients with sepsis. FENDRR can target and bind to miR-424-5p. Both FENDRR and miR-424-5p showed significant diagnostic potential in sepsis and their combination significantly improved the diagnostic efficiency. FENDRR/miR-424-5p were significantly correlated with WBC, CRP, APACH II, and SOFA of sepsis patients. FENDRR and miR-424-5p were independent risk factors for mortality in sepsis patients. Sepsis patients with high FENDRR levels or low miR-424-5p levels had higher mortality. GO and KEGG enrichment analyses revealed that the targets of miR-424-5p were predominantly associated with cell functions and inflammatory signaling pathways.</div></div><div><h3>Conclusion</h3><div>Upregulated FENDRR and downregulated miR-424-5p expression can serve as biomarkers of sepsis with predictive value on the onset and prognostic outcome. FENDRR and miR-424-5p were correlated with the severity of sepsis and FENDRR can play a function in the sepsis progression via targeting miR-424-5p.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152870"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038191","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}
Pub Date : 2025-01-01DOI: 10.1016/j.imbio.2024.152857
Jinglin Zhao , Liuli Wu , Rupan Zhang , Mei Yuan , Junchao Huang , Xiongfei Jia , Xiaoqin Mao
Sepsis-induced myocardial injury has become a major threat to patient health and safety. Intestinal microbiota imbalance plays a crucial role in sepsis regulation. Using 16srRNA technology, we explored how intestinal colonization of Clostridium butyricum over 28 days impacted mice with LPS-induced sepsis. Significant changes were noted in the gut microbiota of the mice, highlighting that C. butyricum can positively influence the immune state in septic myocardial injury models. The bacterium's ability to prevent intestinal mucosal damage and alleviate the immunosuppressive state during the later stages of sepsis by regulating CD4 + CD25 + FOXP3 + Treg cells is particularly noteworthy. This suggests a therapeutic role for C. butyricum in sepsis management by protecting against myocardial injury and improving immune regulation.
{"title":"Clostridium butyricum attenuates LPS-induced myocardial injury in septic mice by modulating CD4 + CD25 + FOXP3 + Treg","authors":"Jinglin Zhao , Liuli Wu , Rupan Zhang , Mei Yuan , Junchao Huang , Xiongfei Jia , Xiaoqin Mao","doi":"10.1016/j.imbio.2024.152857","DOIUrl":"10.1016/j.imbio.2024.152857","url":null,"abstract":"<div><div>Sepsis-induced myocardial injury has become a major threat to patient health and safety. Intestinal microbiota imbalance plays a crucial role in sepsis regulation. Using 16srRNA technology, we explored how intestinal colonization of <em>Clostridium butyricum</em> over 28 days impacted mice with LPS-induced sepsis. Significant changes were noted in the gut microbiota of the mice, highlighting that <em>C. butyricum</em> can positively influence the immune state in septic myocardial injury models. The bacterium's ability to prevent intestinal mucosal damage and alleviate the immunosuppressive state during the later stages of sepsis by regulating CD4 + CD25 + FOXP3 + Treg cells is particularly noteworthy. This suggests a therapeutic role for <em>C. butyricum</em> in sepsis management by protecting against myocardial injury and improving immune regulation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152857"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791609","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}
Pub Date : 2025-01-01DOI: 10.1016/j.imbio.2025.152868
Aya El Gendy , Fawzia Hassan Abo Ali , Shereen A. Baioumy , Sara I. Taha , Mahy El -Bassiouny , Osama M. Abdel Latif
Background
Chronic spontaneous urticaria (CSU) is a persistent skin condition with no known cause or trigger. The unpredictability of CSU attacks lowers patients' quality of life. NOD-like receptor pyrin domain containing 3 (NLRP3) gene dysregulation can result in numerous immunological and inflammatory diseases.
Objective
This case-control study aimed to determine the association between the NLRP3 inflammasome (rs10754558) single nucleotide polymorphism (SNP) and the occurrence, severity and etiology of CSU.
Methods
Each study group included 62 participants; all were subjected to CSU severity evaluation by the urticaria activity score (UAS), autologous serum skin testing (ASST) and NLRP3 (rs10754558) genotyping.
Results
The NLRP3 (rs10754558) CG genotype was the most predominant in both study groups, followed by the CC genotype (41.9 %) in the CSU group and the GG genotype (25.8 %) in the control group. Most of the CSU group (66.1 %) had the C allele, compared to most controls (53.2 %) with the G allele. The frequency of NLRP3 (rs10754558) genotypes and alleles did not differ significantly according to the severity of CSU by UAS (P > 0.05). The prevalence of the CC genotype was significantly higher among the ASST-positive CSU patients. The C allele elevated the likelihood of positive ASST in CSU patients by 21 times, suggesting the autoimmune theory of CSU. None of the ASST-positive patients had the GG genotype.
Conclusion
The NLRP3 inflammasome (rs10754558) C allele may be associated with CSU risk but not severity by UAS. It may also be associated with ASST positivity which suggests a connection between the C-allele and the autoimmune notion of CSU.
{"title":"NOD-like receptor family pyrin domain containing 3 (rs10754558) gene polymorphism in chronic spontaneous urticaria: A pilot case-control study","authors":"Aya El Gendy , Fawzia Hassan Abo Ali , Shereen A. Baioumy , Sara I. Taha , Mahy El -Bassiouny , Osama M. Abdel Latif","doi":"10.1016/j.imbio.2025.152868","DOIUrl":"10.1016/j.imbio.2025.152868","url":null,"abstract":"<div><h3>Background</h3><div>Chronic spontaneous urticaria (CSU) is a persistent skin condition with no known cause or trigger. The unpredictability of CSU attacks lowers patients' quality of life. NOD-like receptor pyrin domain containing 3 (NLRP3) gene dysregulation can result in numerous immunological and inflammatory diseases.</div></div><div><h3>Objective</h3><div>This case-control study aimed to determine the association between the NLRP3 inflammasome (rs10754558) single nucleotide polymorphism (SNP) and the occurrence, severity and etiology of CSU.</div></div><div><h3>Methods</h3><div>Each study group included 62 participants; all were subjected to CSU severity evaluation by the urticaria activity score (UAS), autologous serum skin testing (ASST) and NLRP3 (rs10754558) genotyping.</div></div><div><h3>Results</h3><div>The NLRP3 (rs10754558) CG genotype was the most predominant in both study groups, followed by the CC genotype (41.9 %) in the CSU group and the GG genotype (25.8 %) in the control group. Most of the CSU group (66.1 %) had the C allele, compared to most controls (53.2 %) with the G allele. The frequency of NLRP3 (rs10754558) genotypes and alleles did not differ significantly according to the severity of CSU by UAS (<em>P</em> > 0.05). The prevalence of the CC genotype was significantly higher among the ASST-positive CSU patients. The C allele elevated the likelihood of positive ASST in CSU patients by 21 times, suggesting the autoimmune theory of CSU. None of the ASST-positive patients had the GG genotype.</div></div><div><h3>Conclusion</h3><div>The NLRP3 inflammasome (rs10754558) C allele may be associated with CSU risk but not severity by UAS. It may also be associated with ASST positivity which suggests a connection between the C-allele and the autoimmune notion of CSU.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152868"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004818","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}
Pub Date : 2025-01-01DOI: 10.1016/j.imbio.2024.152863
Qin Si , Lu Yang , Jie Liu , Hui Liu , Ruifang Bu , Na Cui
Background
A key factor underlying the failure of Chimeric Antigen Receptor-T Cell (CAR-T) therapy in ovarian cancer (OC) is the presence of an immunosuppressive tumor microenvironment, which is intricately linked to M2 polarization among tumor-infiltrating macrophages. P2X7 receptor has been previously documented as expressed within these macrophages and its correlation with M2 polarization is evident. This investigation scrutinizes whether silencing of P2X7 receptor within macrophages could lead to augmented anti-tumor potency of CAR-T.
Method
Human peripheral blood mononuclear cells were artificially differentiated into macrophages or M2 macrophage in vitro. After silencing P2X7 receptor and/or overexpressing STAT6 within macrophages, the M1 and M2 markers were evaluated via flow cytometry, ELISA, and qRT-PCR. Additionally, the phosphorylation level of STAT6 was monitored by western blot. We engineered CAR-T cells targeting the non-functional P2X7 (nfP2X7) receptor, and co-cultured them with macrophages silencing P2X7 receptor along with OC cells. The anti-tumor effect of these CAR-T cells was assessed through evaluating OC cell viability, lactate dehydrogenase release, and IFN-γ levels.
Result
P2X7 receptor silencing promotes M1 macrophage marker expression (CD86, TNF-α, IL-6, IL-1β), diminishes M2 macrophage marker expression (CD206 and IL-10) and suppresses STAT6 phosphorylation, whereas STAT6 overexpression reverses these phenomena. Furthermore, M2 macrophage suppresses the toxic effect of CAR-T cells on OC cells, while silencing the P2X7 receptor nullifies the immunosuppressive effect of M2 macrophages on CAR-T cells.
Conclusion
Silencing P2X7 receptor can reverse M2 macrophage polarization by suppressing STAT6 activation, thereby enhancing the anti-tumor efficacy of CAR-T cells targeting nfP2X7 receptor in OC cell lines.
{"title":"Nucleotide receptor P2X7/STAT6 pathway regulates macrophage M2 polarization and its application in CAR-T immunotherapy","authors":"Qin Si , Lu Yang , Jie Liu , Hui Liu , Ruifang Bu , Na Cui","doi":"10.1016/j.imbio.2024.152863","DOIUrl":"10.1016/j.imbio.2024.152863","url":null,"abstract":"<div><h3>Background</h3><div>A key factor underlying the failure of Chimeric Antigen Receptor-T Cell (CAR-T) therapy in ovarian cancer (OC) is the presence of an immunosuppressive tumor microenvironment, which is intricately linked to M2 polarization among tumor-infiltrating macrophages. P2X7 receptor has been previously documented as expressed within these macrophages and its correlation with M2 polarization is evident. This investigation scrutinizes whether silencing of P2X7 receptor within macrophages could lead to augmented anti-tumor potency of CAR-T.</div></div><div><h3>Method</h3><div>Human peripheral blood mononuclear cells were artificially differentiated into macrophages or M2 macrophage in vitro. After silencing P2X7 receptor and/or overexpressing STAT6 within macrophages, the M1 and M2 markers were evaluated via flow cytometry, ELISA, and qRT-PCR. Additionally, the phosphorylation level of STAT6 was monitored by western blot. We engineered CAR-T cells targeting the non-functional P2X7 (nfP2X7) receptor, and co-cultured them with macrophages silencing P2X7 receptor along with OC cells. The anti-tumor effect of these CAR-T cells was assessed through evaluating OC cell viability, lactate dehydrogenase release, and IFN-γ levels.</div></div><div><h3>Result</h3><div>P2X7 receptor silencing promotes M1 macrophage marker expression (CD86, TNF-α, IL-6, IL-1β), diminishes M2 macrophage marker expression (CD206 and IL-10) and suppresses STAT6 phosphorylation, whereas STAT6 overexpression reverses these phenomena. Furthermore, M2 macrophage suppresses the toxic effect of CAR-T cells on OC cells, while silencing the P2X7 receptor nullifies the immunosuppressive effect of M2 macrophages on CAR-T cells.</div></div><div><h3>Conclusion</h3><div>Silencing P2X7 receptor can reverse M2 macrophage polarization by suppressing STAT6 activation, thereby enhancing the anti-tumor efficacy of CAR-T cells targeting nfP2X7 receptor in OC cell lines.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152863"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853936","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}
Pub Date : 2025-01-01DOI: 10.1016/j.imbio.2024.152862
Min Li , Wenjia Tong , Chao Dai , Guoping Lu , Danqun Jin , Fang Deng
Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.
{"title":"Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway","authors":"Min Li , Wenjia Tong , Chao Dai , Guoping Lu , Danqun Jin , Fang Deng","doi":"10.1016/j.imbio.2024.152862","DOIUrl":"10.1016/j.imbio.2024.152862","url":null,"abstract":"<div><div>Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152862"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903046","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}
Pub Date : 2025-01-01DOI: 10.1016/j.imbio.2024.152861
Shan Chen, Jian Liu, Lilei Zhu
Macrophages play a pivotal role in regulating inflammatory response in periodontitis, a condition characterized by excessive osteoclast differentiation. This study aimed to investigate whether exosomes derived from M2 macrophages regulate osteoclast differentiation and to identify the underlying molecular mechanisms. Exosomes were isolated from M2 macrophages and used to treat osteoclasts. Osteoclastogenesis was assessed using tartrate-resistant acid phosphatase staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The molecular mechanism was evaluated using microarray analysis, RT-qPCR, dual-luciferase reporter analysis, and RNA pull-down assay. The results showed that exosomes from M2 macrophages inhibited receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclast differentiation. Additionally, miR-1227-5p expression in osteoclasts was increased after treatment with exosomes, and inhibition of miR-1227-5p counteracted the suppressive effects of exosomes on osteoclastogenesis. Moreover, OSCAR is a target of miR-1227-5p. In conclusion, exosomal miR-1227-5p suppresses osteoclast differentiation, potentially via targeting OSCAR. These findings provide new insights into the pathogenesis of periodontitis.
{"title":"M2-like macrophage-derived exosomes inhibit osteoclastogenesis via releasing miR-1227-5p","authors":"Shan Chen, Jian Liu, Lilei Zhu","doi":"10.1016/j.imbio.2024.152861","DOIUrl":"10.1016/j.imbio.2024.152861","url":null,"abstract":"<div><div>Macrophages play a pivotal role in regulating inflammatory response in periodontitis, a condition characterized by excessive osteoclast differentiation. This study aimed to investigate whether exosomes derived from M2 macrophages regulate osteoclast differentiation and to identify the underlying molecular mechanisms. Exosomes were isolated from M2 macrophages and used to treat osteoclasts. Osteoclastogenesis was assessed using tartrate-resistant acid phosphatase staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The molecular mechanism was evaluated using microarray analysis, RT-qPCR, dual-luciferase reporter analysis, and RNA pull-down assay. The results showed that exosomes from M2 macrophages inhibited receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclast differentiation. Additionally, miR-1227-5p expression in osteoclasts was increased after treatment with exosomes, and inhibition of miR-1227-5p counteracted the suppressive effects of exosomes on osteoclastogenesis. Moreover, OSCAR is a target of miR-1227-5p. In conclusion, exosomal miR-1227-5p suppresses osteoclast differentiation, potentially via targeting OSCAR. These findings provide new insights into the pathogenesis of periodontitis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152861"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864128","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}
Pub Date : 2025-01-01DOI: 10.1016/j.imbio.2024.152866
Xiaoping Li , Dan Xue , Qiongying Wei , Xuexue Tan
Tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a powerful strategy in treating malignant tumors, exhibiting efficacy in both first-line and second-line treatments for advanced non-small cell lung cancer (NSCLC). Despite their success, ICIs can lead to adverse reactions, including interstitial lung disease (ILD), with an incidence ranging from 2.7 % to 20.0 %. The lack of clear correlations with dosage, duration, or drug efficacy, coupled with nonspecific clinical manifestations, poses challenges in timely diagnosis and effective management. This study examined the association between ICIs-related ILD and serum levels of KL-6 and inflammatory markers in NSCLC patients. A total of 382 NSCLC patients with squamous cell carcinoma (SQC, n = 81), adenocarcinoma (ACA, n = 132), and large cell carcinoma (LCC, n = 169) were included, of whom 191 developed ILD following ICIs treatment. Serum KL-6, TNF-α, IL-8, and IL-6 were quantified using ELISA. Results showed significantly elevated serum KL-6 levels in ILD patients (759.35 ± 214.14 U/mL) compared to those without ILD (270.81 ± 124.98 U/mL). Cancer subtype analysis revealed increased KL-6 levels across SQC, ACA, and LCC ILD patients (SQC: 645.89 ± 255.07, ACA: 797.39 ± 192.30, LCC: 783.57 ± 191.21; p < 0.001). ROC analysis identified diagnostic thresholds for KL-6: 277.4 U/mL for SQC (sensitivity 0.9756, specificity 0.8250), 346.9 U/mL for ACA (sensitivity 0.9583, specificity 0.8333), and 281.3 U/mL for LCC (sensitivity 0.9873, specificity 0.6111). Correlation analysis showed a significant relationship between KL-6 and TNF-α (r = 0.4626, p = 0.0023), IL-8 (r = 0.5584, p = 0.0001), and IL-6 (r = 0.5336, p = 0.0003) in SQC ILD patients. These findings suggest that elevated KL-6 levels and inflammatory markers are indicative of ILD in ICIs-treated NSCLC patients, with potential diagnostic implications across cancer subtypes.
肿瘤免疫治疗，特别是免疫检查点抑制剂（ICIs），已经成为治疗恶性肿瘤的一种强有力的策略，在晚期非小细胞肺癌（NSCLC）的一线和二线治疗中都显示出疗效。尽管ICIs取得了成功，但也可能导致不良反应，包括间质性肺疾病（ILD），其发病率在2.7%至20.0%之间。缺乏与剂量、持续时间或药物疗效的明确相关性，加上非特异性临床表现，给及时诊断和有效管理带来了挑战。本研究探讨了非小细胞肺癌患者中icis相关ILD与血清KL-6和炎症标志物水平之间的关系。共纳入382例合并鳞状细胞癌（SQC, n = 81）、腺癌（ACA, n = 132）和大细胞癌（LCC, n = 169）的NSCLC患者，其中191例在ICIs治疗后发生ILD。ELISA法测定血清KL-6、TNF-α、IL-8、IL-6含量。结果显示，ILD患者血清KL-6水平（759.35±214.14 U/mL）明显高于非ILD患者（270.81±124.98 U/mL）。癌症亚型分析显示，在SQC、ACA和LCC患者中，KL-6水平升高(SQC: 645.89±255.07,ACA: 797.39±192.30,LCC: 783.57±191.21；p
{"title":"Serum KL-6 levels reflect the severity of interstitial lung disease caused by immune checkpoint inhibitors","authors":"Xiaoping Li , Dan Xue , Qiongying Wei , Xuexue Tan","doi":"10.1016/j.imbio.2024.152866","DOIUrl":"10.1016/j.imbio.2024.152866","url":null,"abstract":"<div><div>Tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a powerful strategy in treating malignant tumors, exhibiting efficacy in both first-line and second-line treatments for advanced non-small cell lung cancer (NSCLC). Despite their success, ICIs can lead to adverse reactions, including interstitial lung disease (ILD), with an incidence ranging from 2.7 % to 20.0 %. The lack of clear correlations with dosage, duration, or drug efficacy, coupled with nonspecific clinical manifestations, poses challenges in timely diagnosis and effective management. This study examined the association between ICIs-related ILD and serum levels of KL-6 and inflammatory markers in NSCLC patients. A total of 382 NSCLC patients with squamous cell carcinoma (SQC, <em>n</em> = 81), adenocarcinoma (ACA, <em>n</em> = 132), and large cell carcinoma (LCC, <em>n</em> = 169) were included, of whom 191 developed ILD following ICIs treatment. Serum KL-6, TNF-α, IL-8, and IL-6 were quantified using ELISA. Results showed significantly elevated serum KL-6 levels in ILD patients (759.35 ± 214.14 U/mL) compared to those without ILD (270.81 ± 124.98 U/mL). Cancer subtype analysis revealed increased KL-6 levels across SQC, ACA, and LCC ILD patients (SQC: 645.89 ± 255.07, ACA: 797.39 ± 192.30, LCC: 783.57 ± 191.21; <em>p</em> < 0.001). ROC analysis identified diagnostic thresholds for KL-6: 277.4 U/mL for SQC (sensitivity 0.9756, specificity 0.8250), 346.9 U/mL for ACA (sensitivity 0.9583, specificity 0.8333), and 281.3 U/mL for LCC (sensitivity 0.9873, specificity 0.6111). Correlation analysis showed a significant relationship between KL-6 and TNF-α (<em>r</em> = 0.4626, <em>p</em> = 0.0023), IL-8 (<em>r</em> = 0.5584, <em>p</em> = 0.0001), and IL-6 (<em>r</em> = 0.5336, <em>p</em> = 0.0003) in SQC ILD patients. These findings suggest that elevated KL-6 levels and inflammatory markers are indicative of ILD in ICIs-treated NSCLC patients, with potential diagnostic implications across cancer subtypes.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152866"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970672","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}
Gastric cancer (GC) remains a serious health concern and is characterized by a multifactorial etiology involving both genetic and epigenetic factors. The aim of the current study was to examine the relationship between Human leukocyte antigen (HLA)-G 3’UTR polymorphisms and the expression of HLA-G in both tumor tissues and plasma samples from patients with GC in the Tunisian population.
Methods
HLA-G 3’UTR polymorphisms (14pb Insertion/deletion and + 3142C/G) were identified by polymerase chain reaction (PCR) or Sanger sequencing. Plasma levels of sHLA-G (total sHLA-G, shed HLA-G1 and HLA-G5) were determined. Immunohistochemistry was used to evaluate the expression of HLA-G in tumor tissues.
Results
The Del/Del genotype and Del allele frequencies were different between GC patients and healthy donors (HD) (OR [95 % CI] = 2.483 [1.070–5.410], p = 0.025 vs. OR [95 % CI] = 1.537 [0.924–2.584], p = 0.099; respectively). The C/C genotype and C allele frequencies were significantly greater in GC patients than in HD (OR [95 % CI] = 2.269[0.1.070–4.904], p = 0.033 vs. OR [95 % CI] = 1.746[1.045–2.878], p = 0.034; respectively). Interestingly, the Del/Del genotype and Del allele were significantly associated with an increased risk of GC in patients aged ≥55 years at diagnosis. HLA-G was highly expressed in GC tissues, particularly in tissues with advanced tumor invasion (T3 + T4). Compared with HD, GC patients had higher soluble HLA-G, shed HLA-G1 and HLA-G5 levels (Mann-Whitney: p = 0.001, p = 0.001 and p = 0.643, respectively). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele was significantly associated with reduced overall survival (OS) in GC patients at advanced stages III + IV (p = 0.043).
Conclusions
These results suggest that HLA-G 3’UTR polymorphisms are associated with GC susceptibility in Tunisian population. The expression of HLA-G in both the tissue and plasma may play an important role in the development and progression of GC. Therefore, the current study supported the recommendation of investigating HLA-G 3’UTR polymorphisms in GC and indicated that HLA-G molecules could serve as promising therapeutic targets in GC.
背景：胃癌（GC）仍然是一个严重的健康问题，其特点是涉及遗传和表观遗传因素的多因素病因。当前研究的目的是检查突尼斯人群中胃癌患者肿瘤组织和血浆样本中人类白细胞抗原(HLA)-G 3'UTR多态性与HLA-G表达之间的关系。方法：采用聚合酶链反应（PCR）或Sanger测序方法鉴定HLA-G 3'UTR多态性（14pb插入/缺失和+ 3142C/G）。测定血浆sHLA-G水平（总sHLA-G、脱落HLA-G1和HLA-G5）。免疫组化法检测肿瘤组织中HLA-G的表达。结果：GC患者与健康供者（HD）的Del/Del基因型及Del等位基因频率差异有统计学意义(OR [95% CI] = 2.483 [1.070 ~ 5.410], p = 0.025 vs. OR [95% CI] = 1.537 [0.924 ~ 2.584], p = 0.099；分别)。GC患者C/C基因型和C等位基因频率显著高于HD患者(OR [95% CI] = 2.269[0.1.070-4.904], p = 0.033 vs. OR [95% CI] = 1.746[1.045-2.878], p = 0.034；分别)。有趣的是，在诊断时年龄≥55岁的患者中，Del/Del基因型和Del等位基因与GC风险增加显著相关。HLA-G在胃癌组织中高表达，特别是在晚期肿瘤侵袭组织（T3 + T4）中。与HD患者相比，GC患者可溶性HLA-G、脱落HLA-G1和脱落HLA-G5水平较高（Mann-Whitney: p = 0.001、p = 0.001和p = 0.643）。Kaplan-Meier分析患者生存评估显示，Del等位基因与晚期III + IV期GC患者总生存（OS）降低显著相关（p = 0.043）。结论：这些结果表明hla - g3 ' utr多态性与突尼斯人群的GC易感性相关。HLA-G在组织和血浆中的表达可能在GC的发生发展中起重要作用。因此，本研究支持研究HLA-G 3'UTR在胃癌中的多态性的建议，并提示HLA-G分子可能成为胃癌的有希望的治疗靶点。
{"title":"Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis","authors":"Ines Zemni , Daria Bortolotti , Sabrine Dhouioui , Sana Baroudi , Malek Ferjani , Inès Nasri , Yosr Zenzri , Md Ataur Rahman , Abdel Halim Harrath , Roberta Rizzo , Nadia Boujelbene , Inès Zidi","doi":"10.1016/j.imbio.2024.152864","DOIUrl":"10.1016/j.imbio.2024.152864","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) remains a serious health concern and is characterized by a multifactorial etiology involving both genetic and epigenetic factors. The aim of the current study was to examine the relationship between Human leukocyte antigen (HLA)-G 3’UTR polymorphisms and the expression of HLA-G in both tumor tissues and plasma samples from patients with GC in the Tunisian population.</div></div><div><h3>Methods</h3><div>HLA-G 3’UTR polymorphisms (14pb Insertion/deletion and + 3142C/G) were identified by polymerase chain reaction (PCR) or Sanger sequencing. Plasma levels of sHLA-G (total sHLA-G, shed HLA-G1 and HLA-G5) were determined. Immunohistochemistry was used to evaluate the expression of HLA-G in tumor tissues.</div></div><div><h3>Results</h3><div>The Del/Del genotype and Del allele frequencies were different between GC patients and healthy donors (HD) (OR [95 % CI] = 2.483 [1.070–5.410], <em>p</em> = 0.025 vs. OR [95 % CI] = 1.537 [0.924–2.584], <em>p</em> = 0.099; respectively). The C/C genotype and C allele frequencies were significantly greater in GC patients than in HD (OR [95 % CI] = 2.269[0.1.070–4.904], <em>p</em> = 0.033 vs. OR [95 % CI] = 1.746[1.045–2.878], <em>p</em> = 0.034; respectively). Interestingly, the Del/Del genotype and Del allele were significantly associated with an increased risk of GC in patients aged ≥55 years at diagnosis. HLA-G was highly expressed in GC tissues, particularly in tissues with advanced tumor invasion (T3 + T4). Compared with HD, GC patients had higher soluble HLA-G, shed HLA-G1 and HLA-G5 levels (Mann-Whitney: <em>p</em> = 0.001, p = 0.001 and <em>p</em> = 0.643, respectively). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele was significantly associated with reduced overall survival (OS) in GC patients at advanced stages III + IV (<em>p</em> = 0.043).</div></div><div><h3>Conclusions</h3><div>These results suggest that HLA-G 3’UTR polymorphisms are associated with GC susceptibility in Tunisian population. The expression of HLA-G in both the tissue and plasma may play an important role in the development and progression of GC. Therefore, the current study supported the recommendation of investigating HLA-G 3’UTR polymorphisms in GC and indicated that HLA-G molecules could serve as promising therapeutic targets in GC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 1","pages":"Article 152864"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853935","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}
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