Here, we investigated the relationship between the attenuation of lung cancer growth due to oral administration of Euglena gracilis water extract (EWE) and T cell stimulation. Orally administered EWE was revealed to increase PD-1 and PD-L1 mRNA and proteins primarily in tumor-infiltrating lymphocytes (TILs), which was correlated with a significant decrease in the tumor weights in mice. A combination treatment with EWE and anti-PD-1 antibody significantly decreased the growth of murine lung tumors more than treatment with either alone by increasing the number of TILs and attenuating T cell exhaustion. Short-chain fatty acids, which were previously shown to be increased in intestines of mice treated with oral EWE, increased both PD-1 and PD-L1 expression in splenocytes, but not in lung cancer cells in cell culture. These results suggest there is a close relationship between the EWE-induced increase of short-chain fatty acids, the increase of PD-1 expression in TILs, and the attenuation of lung tumor growth. Furthermore, EWE enhances the efficacy of anti-PD-1 antibody-based immune checkpoint blockade therapy against non-small cell lung cancer.
{"title":"A combination treatment with a water extract from Euglena gracilis and anti-PD-1 antibody strongly inhibits growth of lung cancer in mice through stimulating tumor-infiltrating lymphocytes.","authors":"Susumu Ishiguro, Sarah Devader, Caden Blake, Logan Glover, Deepa Upreti, Ayaka Nakashima, Kengo Suzuki, Jeffrey Comer, Masaaki Tamura","doi":"10.1016/j.intimp.2024.113953","DOIUrl":"10.1016/j.intimp.2024.113953","url":null,"abstract":"<p><p>Here, we investigated the relationship between the attenuation of lung cancer growth due to oral administration of Euglena gracilis water extract (EWE) and T cell stimulation. Orally administered EWE was revealed to increase PD-1 and PD-L1 mRNA and proteins primarily in tumor-infiltrating lymphocytes (TILs), which was correlated with a significant decrease in the tumor weights in mice. A combination treatment with EWE and anti-PD-1 antibody significantly decreased the growth of murine lung tumors more than treatment with either alone by increasing the number of TILs and attenuating T cell exhaustion. Short-chain fatty acids, which were previously shown to be increased in intestines of mice treated with oral EWE, increased both PD-1 and PD-L1 expression in splenocytes, but not in lung cancer cells in cell culture. These results suggest there is a close relationship between the EWE-induced increase of short-chain fatty acids, the increase of PD-1 expression in TILs, and the attenuation of lung tumor growth. Furthermore, EWE enhances the efficacy of anti-PD-1 antibody-based immune checkpoint blockade therapy against non-small cell lung cancer.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"113953"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06Epub Date: 2025-01-12DOI: 10.1016/j.intimp.2025.114027
Hanqing Xu, Yi He, Sheng Chen, Chen Meng, Qingyi Liu, Xiao-Jian Huang, Hong-Bo You
Objective: To study the effect of CCR1 and its ligands on macrophage polarization and evaluate its effect on chondrocytes in relieving the progression of osteoarthritis.
Methods: RAW cells were polarized to M1/M2 subtype, and then different concentrations of BX471 were added to selectively inhibit CCR1. The polarization of the cells was detected by RT-qPCR, immunofluorescence and flow cytometry. CCL5 and CCL7 genes were silenced by SiRNA and its role in macrophage polarization was analyzed. Macrophage conditioned medium was further used to stimulate chondrocytes. Histological observation was carried out on models of medial meniscus (DMM) with or without BX471 treatment.
Results: We found that blocking of CCR1 and silencing of its ligand, CCL5 and CCL7, reduced the polarization of M1 macrophages. In terms of mechanism, we found that blocking CCR1 could reduce the activation of NF-κB pathway and inhibit the phosphorylation of IKK, IκBα and P65. In addition, blocking of CCR1 could also reduce cartilage injury induced by macrophage conditioned medium. In vivo, blocking of CCR1 reduced the infiltration and accumulation of M1 macrophages and alleviated articular cartilage injury.
Conclusion: CCL5/CCL7-CCR1 axis was involved in macrophage polarization, and blocking it could reduce synovitis and alleviate the process of OA.
{"title":"Blocking the CCL5/CCL7-CCR1 axis regulates macrophage polarization through NF-κB pathway to alleviate the progression of osteoarthritis.","authors":"Hanqing Xu, Yi He, Sheng Chen, Chen Meng, Qingyi Liu, Xiao-Jian Huang, Hong-Bo You","doi":"10.1016/j.intimp.2025.114027","DOIUrl":"10.1016/j.intimp.2025.114027","url":null,"abstract":"<p><strong>Objective: </strong>To study the effect of CCR1 and its ligands on macrophage polarization and evaluate its effect on chondrocytes in relieving the progression of osteoarthritis.</p><p><strong>Methods: </strong>RAW cells were polarized to M1/M2 subtype, and then different concentrations of BX471 were added to selectively inhibit CCR1. The polarization of the cells was detected by RT-qPCR, immunofluorescence and flow cytometry. CCL5 and CCL7 genes were silenced by SiRNA and its role in macrophage polarization was analyzed. Macrophage conditioned medium was further used to stimulate chondrocytes. Histological observation was carried out on models of medial meniscus (DMM) with or without BX471 treatment.</p><p><strong>Results: </strong>We found that blocking of CCR1 and silencing of its ligand, CCL5 and CCL7, reduced the polarization of M1 macrophages. In terms of mechanism, we found that blocking CCR1 could reduce the activation of NF-κB pathway and inhibit the phosphorylation of IKK, IκBα and P65. In addition, blocking of CCR1 could also reduce cartilage injury induced by macrophage conditioned medium. In vivo, blocking of CCR1 reduced the infiltration and accumulation of M1 macrophages and alleviated articular cartilage injury.</p><p><strong>Conclusion: </strong>CCL5/CCL7-CCR1 axis was involved in macrophage polarization, and blocking it could reduce synovitis and alleviate the process of OA.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"114027"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.intimp.2024.113989
Chenghua Yan , Wendong Kuang , Xinsheng Liu
Group 2 innate lymphoid cells (ILC2s) produce the type 2 cytokines IL-5 and IL-13 and contribute to type 2 immune responses, such as allergic airway inflammation. However, specific drugs, especially traditional Chinese medicines, that target lung ILC2s have rarely been reported. Here, we demonstrate that triptolide ameliorates allergic airway inflammation by suppressing ILC2 activation. IL-33, which is produced mainly by epithelial cells, is the most powerful cytokine for activating ILC2s. Triptolide-treated ILC2s were found to be functionally impaired in response to interleukin (IL)–33 challenge. RNA-seq analysis revealed that triptolide impaired ILC2 function through inflammation-related signalling pathways. ILC2-related genes were up- and down-regulated under the treatment with TPL such as Adrb2, Nmur1, tnfsf11, IL-5, IL-13, IL-9 and so on. Interestingly, we observed not only preventive but also therapeutic effects of triptolide on allergic airway inflammation, indicating that triptolide may serve as a promising traditional Chinese medicine for the treatment of allergic airway inflammation by targeting ILC2s.
{"title":"Triptolide alleviates allergic airway inflammation by inhibiting group 2 innate lymphoid cell function","authors":"Chenghua Yan , Wendong Kuang , Xinsheng Liu","doi":"10.1016/j.intimp.2024.113989","DOIUrl":"10.1016/j.intimp.2024.113989","url":null,"abstract":"<div><div>Group 2 innate lymphoid cells (ILC2s) produce the type 2 cytokines IL-5 and IL-13 and contribute to type 2 immune responses, such as allergic airway inflammation. However, specific drugs, especially traditional Chinese medicines, that target lung ILC2s have rarely been reported. Here, we demonstrate that triptolide ameliorates allergic airway inflammation by suppressing ILC2 activation. IL-33, which is produced mainly by epithelial cells, is the most powerful cytokine for activating ILC2s. Triptolide-treated ILC2s were found to be functionally impaired in response to interleukin (IL)–33 challenge. RNA-seq analysis revealed that triptolide impaired ILC2 function through inflammation-related signalling pathways. ILC2-related genes were up- and down-regulated under the treatment with TPL such as Adrb2, Nmur1, tnfsf11, IL-5, IL-13, IL-9 and so on. Interestingly, we observed not only preventive but also therapeutic effects of triptolide on allergic airway inflammation, indicating that triptolide may serve as a promising traditional Chinese medicine for the treatment of allergic airway inflammation by targeting ILC2s.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113989"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.intimp.2024.113985
Li-Li Wu , Wei-Dong Shi , Wei-Feng Peng , Guo-Yin Li
Meningitis, characterized by an inflammatory response affecting the membranes surrounding the brain and spinal cord, poses a formidable challenge to global public health. Its etiology spans a spectrum of infectious agents, ranging from bacteria, to viruses, fungi, and parasites. Concurrently, mitochondria—traditionally known as ‘cellular powerhouses’—have emerged as critical players in various essential biological functions, including but not limited to, energy production, metabolic regulation, and cell fate determination. Emerging evidence suggests that mitochondria may play vital roles in the pathogenesis of meningitis. In this review, we delineated the definition, classification, etiology, pathogenesis, and clinical manifestations of meningitis, and elucidated the structure, dynamics and functions of mitochondria. We subsequently delved into the intricate interplay between meningitis and mitochondria, identifying potential therapeutic interventions targeting mitochondria for the first time. With clinical trials on the horizon, our review lays the foundation for a transformative era in meningitis therapeutics, where unraveling the intricate interplay between meningitis and mitochondria offers promise for mitigating neuroinflammation and improving patient outcomes.
{"title":"Unraveling the interplay between meningitis and mitochondria: Etiology, pathogenesis, and therapeutic insights","authors":"Li-Li Wu , Wei-Dong Shi , Wei-Feng Peng , Guo-Yin Li","doi":"10.1016/j.intimp.2024.113985","DOIUrl":"10.1016/j.intimp.2024.113985","url":null,"abstract":"<div><div>Meningitis, characterized by an inflammatory response affecting the membranes surrounding the brain and spinal cord, poses a formidable challenge to global public health. Its etiology spans a spectrum of infectious agents, ranging from bacteria, to viruses, fungi, and parasites. Concurrently, mitochondria—traditionally known as ‘cellular powerhouses’—have emerged as critical players in various essential biological functions, including but not limited to, energy production, metabolic regulation, and cell fate determination. Emerging evidence suggests that mitochondria may play vital roles in the pathogenesis of meningitis. In this review, we delineated the definition, classification, etiology, pathogenesis, and clinical manifestations of meningitis, and elucidated the structure, dynamics and functions of mitochondria. We subsequently delved into the intricate interplay between meningitis and mitochondria, identifying potential therapeutic interventions targeting mitochondria for the first time. With clinical trials on the horizon, our review lays the foundation for a transformative era in meningitis therapeutics, where unraveling the intricate interplay between meningitis and mitochondria offers promise for mitigating neuroinflammation and improving patient outcomes.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113985"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review explores the progressive domain of network pharmacology and its potential to revolutionize therapeutic approaches for Interstitial Lung Diseases (ILDs), a collective term encompassing Interstitial Pneumonia, Pneumoconiosis, Connective Tissue Disease-related ILDs, and Sarcoidosis. The exploration focuses on the profound legacy of traditional medicines, particularly Ayurveda and Traditional Chinese Medicines (TCM), and their largely unexplored capacity in ILD treatment. These ancient healing systems, characterized by their holistic methodologies and multifaceted treatment modalities, offer a promising foundation for discovering innovative therapeutic strategies. Moreover, the review underscores the amalgamation of artificial intelligence (AI) and machine learning (ML) methodologies with bioinformatics, creating a computational synergy capable of deciphering the intricate biological networks associated with ILDs. Network pharmacology has tailored the hypothesis from the conventional “one target, one drug” towards a “network target, multi-component therapeutics” approach. The fusion of traditional literature and computational technology can unveil novel drugs, targets, and pathways, augmenting effective therapies and diminishing adverse effects related to current medications. In conclusion, this review provides a comprehensive exposition of how Network Pharmacology tools can leverage the insights of Ayurveda and TCM to craft efficacious therapeutic solutions for ILDs. It sets the stage for future investigations in this captivating interdisciplinary domain, validating the use of traditional medicines worldwide.
{"title":"Network Pharmacology-driven therapeutic interventions for Interstitial Lung Diseases using Traditional medicines: A Narrative Review","authors":"Megh Pravin Vithalkar , K.S. Sandra , H.B. Bharath , B. Krishnaprasad , S.M. Fayaz , B. Sathyanarayana , Yogendra Nayak","doi":"10.1016/j.intimp.2024.113979","DOIUrl":"10.1016/j.intimp.2024.113979","url":null,"abstract":"<div><div>This review explores the progressive domain of network pharmacology and its potential to revolutionize therapeutic approaches for Interstitial Lung Diseases (ILDs), a collective term encompassing Interstitial Pneumonia, Pneumoconiosis, Connective Tissue Disease-related ILDs, and Sarcoidosis. The exploration focuses on the profound legacy of traditional medicines, particularly Ayurveda and Traditional Chinese Medicines (TCM), and their largely unexplored capacity in ILD treatment. These ancient healing systems, characterized by their holistic methodologies and multifaceted treatment modalities, offer a promising foundation for discovering innovative therapeutic strategies. Moreover, the review underscores the amalgamation of artificial intelligence (AI) and machine learning (ML) methodologies with bioinformatics, creating a computational synergy capable of deciphering the intricate biological networks associated with ILDs. Network pharmacology has tailored the hypothesis from the conventional “one target, one drug” towards a “network target, multi-component therapeutics” approach. The fusion of traditional literature and computational technology can unveil novel drugs, targets, and pathways, augmenting effective therapies and diminishing adverse effects related to current medications. In conclusion, this review provides a comprehensive exposition of how Network Pharmacology tools can leverage the insights of Ayurveda and TCM to craft efficacious therapeutic solutions for ILDs. It sets the stage for future investigations in this captivating interdisciplinary domain, validating the use of traditional medicines worldwide.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113979"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.intimp.2024.113859
Jing Shan , Jie Ding , Da-Jin Li , Xiao-Qiu Wang
Interleukin (IL)-18 is one of the members of IL-1 family cytokines, it was originally named as interferon gamma (IFN-γ) inducing factor. IL-18 is a pleiotropic immune regulator and has a bidirectional regulatory effect on immunity. It exerts a potent pro-inflammatory effect by inducing the expression of IFN-γ, also has an important anti-inflammatory role. In recent years, IL-18 has received widespread attention and become a research hotspot. Previous studies have described the roles of IL-18 in the pathogenesis of many diseases. However, the biologic activities of IL-18 and its role in the reproductive endocrine and reproductive immune related diseases are still not well understood, such as endometriosis (EMS), recurrent spontaneous abortion (RSA), polycystic ovary syndrome (PCOS), and infertility, which are closely related to inflammation and immunity. Here, we reviewed the research progress of IL-18 in these diseases in the past few years. This article provides an overview of the latest knowledge about the roles of IL-18 in these diseases, with a view to providing new possibilities for the diagnosis and treatment of reproductive endocrine and reproductive immune related disorders.
{"title":"The double-edged role of IL-18 in reproductive endocrine and reproductive immune related disorders","authors":"Jing Shan , Jie Ding , Da-Jin Li , Xiao-Qiu Wang","doi":"10.1016/j.intimp.2024.113859","DOIUrl":"10.1016/j.intimp.2024.113859","url":null,"abstract":"<div><div>Interleukin (IL)-18 is one of the members of IL-1 family cytokines, it was originally named as interferon gamma (IFN-γ) inducing factor. IL-18 is a pleiotropic immune regulator and has a bidirectional regulatory effect on immunity. It exerts a potent pro-inflammatory effect by inducing the expression of IFN-γ, also has an important anti-inflammatory role. In recent years, IL-18 has received widespread attention and become a research hotspot. Previous studies have described the roles of IL-18 in the pathogenesis of many diseases. However, the biologic activities of IL-18 and its role in the reproductive endocrine and reproductive immune related diseases are still not well understood, such as endometriosis (EMS), recurrent spontaneous abortion (RSA), polycystic ovary syndrome (PCOS), and infertility, which are closely related to inflammation and immunity. Here, we reviewed the research progress of IL-18 in these diseases in the past few years. This article provides an overview of the latest knowledge about the roles of IL-18 in these diseases, with a view to providing new possibilities for the diagnosis and treatment of reproductive endocrine and reproductive immune related disorders.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113859"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.intimp.2024.113937
Weiting Hu , Wenyu Gong , Fan Yang , Rui Cheng , Gerong Zhang , Lu Gan , Yikun Zhu , Weiwei Qin , Ying Gao , Xing Li , Jing Liu
Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia, elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, β-muricholic acid: β-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).
{"title":"Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice","authors":"Weiting Hu , Wenyu Gong , Fan Yang , Rui Cheng , Gerong Zhang , Lu Gan , Yikun Zhu , Weiwei Qin , Ying Gao , Xing Li , Jing Liu","doi":"10.1016/j.intimp.2024.113937","DOIUrl":"10.1016/j.intimp.2024.113937","url":null,"abstract":"<div><div>Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as <em>Akkermansia</em>, elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, β-muricholic acid: β-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113937"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.intimp.2025.114050
Han Yue , Xiaoling Zhang , Zhiyi Zhao , Song Gong , Shiying Shao
Recent studies demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) have promising prospects in promoting wound healing. In this study, we intend to investigate the pro-healing effect and potential molecular mechanism of topical administration of GLP-1RA liraglutide on wounds in normoglycemic mice. Two full-thickness wounds were created on the back of the C57BL/6 mice. The “lower” wounds were topically infiltrated with liraglutide every day after injury; while the “upper” wounds were infiltrated with saline solution. Wound area was measured daily during the 10-day study period. The wound tissue was stained with H&E and immunofluorescence. Western blotting was performed to detect the markers in macrophages. The results showed that topical administration of liraglutide resulted in a rapid reduction of wound size. The capillary density and the expression of vascular endothelial growth factor (VEGF)-A were significantly increased in liraglutide-treated wounds. Findings from immunofluorescence and Western blotting revealed that liraglutide promoted phenotypic polarization of macrophages from M1 to M2. We further identified that M2a macrophages predominantly presented in the early and middle stages of inflammation phase and M2d macrophages presented in the middle and late stages. Our study suggested that GLP-1RA liraglutide could promote wound healing in normoglycemic mice, which is partly attributed to the modulation of the macrophage polarization from M1 subtype to M2 subtype.
{"title":"Pro-healing impact of liraglutide on skin wounds in normoglycemic mice","authors":"Han Yue , Xiaoling Zhang , Zhiyi Zhao , Song Gong , Shiying Shao","doi":"10.1016/j.intimp.2025.114050","DOIUrl":"10.1016/j.intimp.2025.114050","url":null,"abstract":"<div><div>Recent studies demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) have promising prospects in promoting wound healing. In this study, we intend to investigate the pro-healing effect and potential molecular mechanism of topical administration of GLP-1RA liraglutide on wounds in normoglycemic mice. Two full-thickness wounds were created on the back of the C57BL/6 mice. The “lower” wounds were topically infiltrated with liraglutide every day after injury; while the “upper” wounds were infiltrated with saline solution. Wound area was measured daily during the 10-day study period. The wound tissue was stained with H&E and immunofluorescence. Western blotting was performed to detect the markers in macrophages. The results showed that topical administration of liraglutide resulted in a rapid reduction of wound size. The capillary density and the expression of vascular endothelial growth factor (VEGF)-A were significantly increased in liraglutide-treated wounds. Findings from immunofluorescence and Western blotting revealed that liraglutide promoted phenotypic polarization of macrophages from M1 to M2. We further identified that M2a macrophages predominantly presented in the early and middle stages of inflammation phase and M2d macrophages presented in the middle and late stages. Our study suggested that GLP-1RA liraglutide could promote wound healing in normoglycemic mice, which is partly attributed to the modulation of the macrophage polarization from M1 subtype to M2 subtype.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114050"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06Epub Date: 2025-01-12DOI: 10.1016/j.intimp.2025.114034
Xiaoyu Cai, Fujia Ren, Yao Yao
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, damage, and loss of function. In recent years, the role of gut microbiota and its metabolites in immune regulation has attracted increasing attention. The gut microbiota influences the host immune system's homeostasis through various mechanisms, regulating the differentiation, function, and immune tolerance of immune cells. Dysbiosis of the gut microbiota in RA patients is closely associated with abnormal activation of immune cells and excessive secretion of inflammatory cytokines. Metabolites produced by the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and amino acid metabolites, play a critical role in immune responses, regulating the functions of immune cells like T cells, B cells, and macrophages, and inhibiting the release of pro-inflammatory cytokines. Restoring the balance of the gut microbiota and optimizing the production of metabolic products may become a new strategy for RA treatment. This review discusses the role of gut microbiota and its metabolites in the immune response of RA, exploring how they influence the immunopathological process of RA through the regulation of immune cells and key immune factors. It also provides a theoretical basis for future therapeutic strategies based on gut microbiota modulation.
{"title":"Gut microbiota and their metabolites in the immune response of rheumatoid arthritis: Therapeutic potential and future directions.","authors":"Xiaoyu Cai, Fujia Ren, Yao Yao","doi":"10.1016/j.intimp.2025.114034","DOIUrl":"10.1016/j.intimp.2025.114034","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, damage, and loss of function. In recent years, the role of gut microbiota and its metabolites in immune regulation has attracted increasing attention. The gut microbiota influences the host immune system's homeostasis through various mechanisms, regulating the differentiation, function, and immune tolerance of immune cells. Dysbiosis of the gut microbiota in RA patients is closely associated with abnormal activation of immune cells and excessive secretion of inflammatory cytokines. Metabolites produced by the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and amino acid metabolites, play a critical role in immune responses, regulating the functions of immune cells like T cells, B cells, and macrophages, and inhibiting the release of pro-inflammatory cytokines. Restoring the balance of the gut microbiota and optimizing the production of metabolic products may become a new strategy for RA treatment. This review discusses the role of gut microbiota and its metabolites in the immune response of RA, exploring how they influence the immunopathological process of RA through the regulation of immune cells and key immune factors. It also provides a theoretical basis for future therapeutic strategies based on gut microbiota modulation.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"114034"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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