International immunopharmacology最新文献

{"title":"Exosomes derived from primary cartilage stem/progenitor cells promote the repair of osteoarthritic chondrocytes by modulating immune responses","authors":"","doi":"10.1016/j.intimp.2024.113397","DOIUrl":"10.1016/j.intimp.2024.113397","url":null,"abstract":"<div><h3>Background</h3><div>Exosomes derived from primary chondrogenic stem/progenitor cells (CSPCs-EXOs) show promise in cartilage repair due to their immunomodulatory and regenerative properties. However, their specific therapeutic potential in osteoarthritis (OA), especially in modulating immune responses and enhancing chondrocyte function, requires further exploration. This study aims to clarify CSPCs-EXOs’ effects on OA by investigating their role in chondrocyte proliferation, migration, inflammation inhibition, and cartilage regeneration.</div></div><div><h3>Methods</h3><div>A rat model of osteoarthritis was established using monosodium iodoacetate (MIA). CSPCs-EXOs were isolated and characterized before being administered to the OA rats. Comprehensive transcriptomic analysis was conducted to identify differentially expressed genes (DEGs) and signaling pathways influenced by CSPCs-EXOs. Histopathological evaluation of cartilage tissue, immunohistochemistry, and in vitro assays were performed to assess chondrocyte proliferation, migration, inflammation, and intracellular environmental changes.</div></div><div><h3>Results</h3><div>CSPCs-EXOs treatment significantly reduced OA-induced cartilage damage, shown by improved histopathological features, increased chondrocyte proliferation, migration, and enhanced cartilage matrix integrity. CSPCs-EXOs uniquely modulated immune pathways and enhanced cellular repair, setting them apart from traditional treatments. Transcriptomic analysis revealed regulation of immune response, inflammation, oxidative stress, and DNA repair pathways. CSPCs-EXOs downregulated inflammatory cytokines (TNF, IL-17) and upregulated pathways for cellular proliferation, migration, and metabolism. They also altered splicing patterns of DNA repair enzymes, indicating a role in boosting repair mechanisms.</div></div><div><h3>Conclusions</h3><div>CSPCs-EXOs promote cartilage repair in osteoarthritis by modulating immune responses, inhibiting inflammation, and improving the intracellular environment. These findings emphasize their innovative therapeutic potential and offer key insights into their regenerative mechanisms, positioning CSPCs-EXOs as a promising strategy for OA treatment and a foundation for future clinical applications in cartilage tissue engineering and regenerative medicine.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499804","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}

{"title":"CD36 deficiency protects lipopolysaccharide-induced sepsis via inhibiting CerS6-mediated endoplasmic reticulum stress","authors":"","doi":"10.1016/j.intimp.2024.113441","DOIUrl":"10.1016/j.intimp.2024.113441","url":null,"abstract":"<div><div>The type 2 scavenger receptor CD36 functions not only as a long chain fatty acid transporter, but also as a pro-inflammatory mediator. Ceramide is the simple <em>N</em>-acylated form of sphingosine and exerts distinct biological activity depending on its acyl chain length. Six ceramide synthases (CerS) in mammals determine the chain length of ceramide species, and CerS6 mainly produces C16-ceramide. Endotoxin-induced septic shock shows high mortality, but the pathophysiologic role of sphingolipids involved in this process has been hardly investigated. This paper aims to highlight the different role of CerS isoforms in endotoxin-induced inflammatory responses and the regulatory role of CD36 in CerS6 protein degradation with an emphasis as the potential therapeutic candidates in humans. Lipopolysaccharide (LPS), the endotoxin of the Gram-negative bacterial cell wall, was treated to induce endotoxin-induced inflammation both <em>in vitro</em> and <em>in vivo</em>. CerS6-derived C16-ceramide propagated LPS-induced inflammatory responses activating various intracellular signaling pathways, such as mitogen-activated protein kinase and nuclear factor-κB, resulting in the formation of inflammasome complex and pro-inflammatory cytokines. Mechanistically, CerS6-derived C16-ceramide augmented inflammatory responses via endoplasmic reticulum stress, and CerS6 protein stability was regulated by CD36. Finally, CerS6 protein expression and LPS-induced lethality were strikingly reduced in CD36 knockout mice. Collectively, our findings show that CerS6-derived C16-ceramide plays a pivotal role in endotoxin-induced inflammation and suggest CerS6 and its regulator CD36 as possible targets for therapy under life-threatening inflammation such as septic shock.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499792","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}

{"title":"Corrigendum to \"Icosapent ethyl alleviates acetic acid-induced ulcerative colitis via modulation of SIRT1 signaling pathway in rats\" [Int. Immunopharmacol. 115 (2023) 109621].","authors":"Ahmed Ahmed Abdelsameea, Amira Ebrahim Alsemeh, Nadia Alabassery, Walaa Samy, Amal Fawzy, Noha A T Abbas","doi":"10.1016/j.intimp.2024.112647","DOIUrl":"10.1016/j.intimp.2024.112647","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897357","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}

{"title":"Anti-inflammatory effects of heat-killed Lactiplantibacillus argentoratensis BBLB001 on a gut inflammation co-culture cell model and dextran sulfate sodium-induced colitis mouse model","authors":"","doi":"10.1016/j.intimp.2024.113408","DOIUrl":"10.1016/j.intimp.2024.113408","url":null,"abstract":"<div><div>Dysbiosis caused by dietary changes can alter the intestinal bacterial species and is closely associated with inflammatory bowel disease (IBD). Among the possible treatment options, postbiotics, which act to balance the constituent intestinal microflora, have gained substantial attention. Herein, we investigated the anti-inflammatory effects of heat-killed <em>Lactiplantibacillus argentoratensis</em> (hk-LA) BBLB001 isolated from a marine environment using both cell (Caco2/RAW264.7 cell co-culture) and animal (dextran sodium sulfate [DSS]-induced colitis in mice) models. hk-LA BBLB001 markedly reduced IL-8 secretion in Caco-2 cell culture medium after lipopolysaccharide-mediated stimulation of RAW264.7 cells by enhancing the expression of cell adhesion factors.The body weight loss, reduced inflammatory cytokine levels in the serum and colon tissues, colon shortening, and myeloperoxidase activation caused by DSS in mice were alleviated by hk-LA BBLB001. Similar to that in the intestinal cell model, the gene and protein expressions of cell adhesion molecules in the colon tissue were increased upon hk-LA BBLB001 treatment in DSS-induced colitis mice. We observed increased mucin expression and secretory IgA concentration in colon tissues, suggesting that hk-LA BBLB001 intake may benefit pathogen defense and the regulation of intestinal commensal bacteria. Thus, hk-LA BBLB001 may serve as an instrumental postbiotic material in IBD treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499789","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}

{"title":"Corrigendum to \"Maackiain protects against sepsis via activating AMPK/Nrf2/HO-1 pathway\" [Int. Immunopharmacol. 108 (2022) 108710].","authors":"Xiaoxue Bai, Yingjie Zhu, Jing Jie, Dan Li, Lei Song, Jingjing Luo","doi":"10.1016/j.intimp.2024.112877","DOIUrl":"10.1016/j.intimp.2024.112877","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912536","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}

{"title":"Quercetin inhibits mitophagy-mediated apoptosis and inflammatory response by targeting the PPARγ/PGC-1α/NF-κB axis to improve acute liver failure","authors":"","doi":"10.1016/j.intimp.2024.113444","DOIUrl":"10.1016/j.intimp.2024.113444","url":null,"abstract":"<div><h3>Background</h3><div>Reactive oxygen species (ROS) from mitochondrial dysfunction are critical in triggering apoptosis and inflammation in acute liver failure (ALF). Quercetin (QUE), an antioxidant, is renowned for its therapeutic effects on<!--> <!-->liver<!--> <!-->diseases. There are no studies on whether QUE regulates mitophagy level in hepatocytes to inhibit ALF.</div></div><div><h3>Objective</h3><div>This study investigates QUE’s protective effects on ALF and elucidates the mechanisms involved.</div></div><div><h3>Methods</h3><div>The ALF and hepatocyte inflammatory injury model was established using LPS and D-Galn. To predict potential targets and mechanisms of QUE in ALF treatment, transcriptomics, network pharmacology, molecular docking techniques, and ChIP were employed. The expression level related to mitophagy, apoptosis, and signaling pathways were detected by CCK8, IHC, IF staining, TUNEL, RT-qPCR, TEM, Western blotting, ELISA, and flow cytometry.</div></div><div><h3>Results</h3><div>Network pharmacology and transcriptomics revealed common targets between QUE and ALF. Enrichment analysis showed that the anti-ALF targets of QUE were significantly associated with mitochondria and NF-κB-related pathways. Subsequent experiments showed that QUE pretreatment significantly alleviated the loss of hepatocyte viability, enhanced mitochondrial membrane potential, activated mitophagy, and promoted the clearance of damaged mitochondria, thereby reducing ROS accumulation, significantly reducing cell apoptosis and inflammatory responses, reducing ALT and AST levels, and improving liver tissue pathology. Mechanistically, molecular docking, DARTS, and CETSA analyses confirmed that QUE directly binds to the PPARγ molecule, which reduced binding to IκB and significantly inhibit the NF-κB pathway to exert its protective effects.</div></div><div><h3>Conclusion</h3><div>In short, our results provide the first evidence that QUE improves acute liver failure by promoting mitophagy through regulating the PPARγ/PGC-1α/NF-κB axis and inhibiting apoptosis and inflammatory responses mediated by mitochondrial dysfunction, which provides evidence for the potential of QUE in the treatment of ALF.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499824","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}

{"title":"Erratum to \"Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia\" [Int. Immunopharmacol. 136 (2024) 112330].","authors":"Lu-Wen Zhang, Chun-Ai Cui, Chao Liu, Lian-Ping Sun, Yi-Nan Ouyang, Long-Fei Li, Dong-Liang Zhang, Hai-Ling Yu","doi":"10.1016/j.intimp.2024.112674","DOIUrl":"10.1016/j.intimp.2024.112674","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982262","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}

{"title":"The triple combination DBDx alleviates cytokine storm and related lung injury","authors":"","doi":"10.1016/j.intimp.2024.113431","DOIUrl":"10.1016/j.intimp.2024.113431","url":null,"abstract":"<div><div>Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499839","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}

{"title":"Corrigendum to \"Betulinic acid isolated from Bacopa monniera (L.) Wettst suppresses lipopolysaccharide stimulated interleukin-6 production through modulation of nuclear factor-κB in peripheral blood mononuclear cells\" [Int. Immunopharmacol. 10/8 (2010) 843-849].","authors":"V Viji, B Shobha, S K Kavitha, M Ratheesh, K Kripa, A Helen","doi":"10.1016/j.intimp.2024.112648","DOIUrl":"10.1016/j.intimp.2024.112648","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897356","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}

{"title":"Targeting metabolic pathway enhance CAR-T potency for solid tumor","authors":"","doi":"10.1016/j.intimp.2024.113412","DOIUrl":"10.1016/j.intimp.2024.113412","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cells have great potential in cancer therapy, particularly in treating hematologic malignancies. However, their efficacy in solid tumors remains limited, with a significant proportion of patients failing to achieve long-term complete remission. One major challenge is the premature exhaustion of CAR-T cells, often due to insufficient metabolic energy. The survival, function and metabolic adaptation of CAR-T cells are key determinants of their therapeutic efficacy. We explore how targeting metabolic pathways in the tumor microenvironment can enhance CAR-T cell therapy by addressing metabolic competition and immunosuppression that impair CAR-T cell function. Tumors undergo metabolically reprogrammed to meet their rapid proliferation, thereby modulating metabolic pathways in immune cells to promote immunosuppression. The distinct metabolic requirements of tumors and T cells create a competitive environment, affecting the efficacy of CAR-T cell therapy. Recent research on glucose, lipid and amino acid metabolism, along with the interactions between tumor and immune cell metabolism, has revealed that targeting these metabolic processes can enhance antitumor immune responses. Combining metabolic interventions with existing antitumor therapies can fulfill the metabolic demands of immune cells, providing new ideas for tumor immunometabolic therapies. This review discusses the latest advances in the immunometabolic mechanisms underlying tumor immunosuppression, their implications for immunotherapy, and summarizes potential metabolic targets to improve the efficacy of CAR-T therapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499828","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}