International immunopharmacology最新文献

{"title":"Neuro-immune regulation in allergic Diseases: Role of neuropeptides.","authors":"Cuiying He, Qian Wang, Jinyan Gao, Hongbing Chen, Ping Tong","doi":"10.1016/j.intimp.2024.113771","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113771","url":null,"abstract":"<p><p>The role of neuro-immune interaction in allergic diseases, a group of common immune system diseases, has garnered increasing attention. Neuropeptides, as a crucial component of neuro-immune crosstalk with local neuroendocrine and signaling functions, play a significant role that must not be overlooked. Neuropeptides are released by neurons and even some immune cells, and mediate neuro-immune crosstalk by activating relevant specific receptors on immune cells. Recent studies have found that neuropeptides have a certain regulatory effect on allergic diseases, which could be beneficial or detrimental for the development of allergic diseases. Nevertheless, the precise mechanism of neuropeptides in allergic diseases remains unclear, particularly in the context of food allergy where their role is poorly understood. This review summarized the interplay between neuropeptides and different immune cells, as well as their current research progress in several common allergic diseases: atopic dermatitis, allergic asthma, and food allergy. It is evident that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuromedin U, exert important regulatory effects on allergic diseases, yet further investigation is required to fully elucidate their mechanisms of action, which may contribute to better understanding of the onset and progression of allergic diseases and finding better immunomodulatory strategies.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113771"},"PeriodicalIF":4.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817906","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 CFTR restoring aggrephagy to suppress HSC activation and alleviate liver fibrosis.","authors":"Lu Zhang, Wei Huang, Tao Ma, Xiang Shi, Jing Chen, Yi-Lin Hu, Yong-Xia Liu, Zhao-Xiu Liu, Cui-Hua Lu","doi":"10.1016/j.intimp.2024.113754","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113754","url":null,"abstract":"<p><strong>Background and aims: </strong>Multiple studies have shown that hepatic fibrosis, a progressive condition that represents the endpoint of various chronic liver diseases, is primarily marked by the extensive activation of hepatic stellate cells (HSCs). However, the exact impact of cystic fibrosis transmembrane conductance regulator (CFTR) on HSCs during the development of hepatic fibrosis remains unclear.</p><p><strong>Methods: </strong>In our study, we measured CFTR levels in tissue samples and in HSCs activated by TGF-β stimulation. We established mouse models of liver fibrosis using carbon tetrachloride (CCl₄) and bile duct ligation (BDL). In vitro, we investigated the specific mechanisms of CFTR action in HSCs by exploring aggrephagy. We employed co-immunoprecipitation (co-IP) experiments to identify potential downstream targets of CFTR. Finally, through rescue experiments, we examined the impact of GTPase-activating protein - binding protein 1 (G3BP1) on CFTR-mediated activation of hepatic stellate cells.</p><p><strong>Result: </strong>In activated HSCs induced by TGF-β, the reduction of CFTR, various liver fibrosis models, and fibrotic tissue samples were identified. In vitro functional experiments confirmed that CFTR promoted the expression of fibrosis-related markers and aggrephagy in HSCs. Mechanistically, we found that CFTR directly interacts with G3BP1, thereby further promoting the TGF-β/Smad2/3 pathway. The inhibition of G3BP1 caused by CFTR knockdown reduced extracellular matrix deposition, contributing to alleviating liver fibrosis.</p><p><strong>Conclusion: </strong>We emphasize that CFTR activates aggrephagy and promotes HSC activation and hepatic fibrosis by targeting G3BP1, participating in the TGF-β/Smad2/3 signaling pathway. Overall, CFTR has been identified as a potential therapeutic target for liver fibrosis.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113754"},"PeriodicalIF":4.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817990","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":"Salicylalazine: A novel therapeutic agent targeting TLR4/NLRP3/GSDMD-mediated pyroptosis in rheumatoid arthritis.","authors":"Sumera Qasim, Fakhria A Al-Joufi, Ambreen Malik Uttra, Hafiza Sara Afzal, Shaimaa R Ahmed","doi":"10.1016/j.intimp.2024.113778","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113778","url":null,"abstract":"<p><strong>Background: </strong>Joint pain and functional impairment are hallmarks of arthritis, a painful inflammatory disease. Salicylalazine (SAZ), an anti-inflammatory compound, has demonstrated promise in modulating inflammation, thereby being selected in the current study to unveil its anti-arthritic potential.</p><p><strong>Objectives: </strong>The aim behind this study was to assess the anti-arthritic properties of salicylalazine via evaluating its impact on paw volume, arthritic scores, oxidative stress indicators, and significant inflammatory mediators.</p><p><strong>Methods: </strong>The arthritic potential of SAZ was estimated first through the formaldehyde (FA) model to screen the most effective dose of SAZ, followed by the Complete Freund's adjuvant (CFA) model. Over a 28-day period, we monitored parameters such as paw edema, arthritic index, body weight, flexion pain, mobility, and stance score. Oxidative stress markers (GSH, CAT, SOD, MDA), serological markers (CRP, RF, anti-CCP), and gene expression of key inflammatory mediators (TLR4, MyD88, NFκB, NLRP3, ASC, IL-1β, IL-18, caspase-1, GSDMD) were assessed.</p><p><strong>Results: </strong>SAZ treatment led to a substantial decrease in paw volume in both arthritis models, with the most pronounced effects observed on day 10 for the formaldehyde model and day 28 for the CFA model (p < 0.001). Additionally, SAZ helped to restore the body's weight and considerably relieved the flexion pain, which led to improvements in both mobility and stance. Moreover, SAZ substantially raised the levels of antioxidant enzymes (GSH, CAT, SOD) and decreased MDA levels, suggesting a reduction in oxidative stress. Also with SAZ, there was a substantial (p < 0.001) decrease in the expression of pyroptotic mediators. Serological markers of inflammation, including CRP, RF, and anti-CCP levels, were also restored by SAZ administration.</p><p><strong>Conclusion: </strong>In a nutshell, SAZ achieved significant anti-arthritic benefits, most likely via the modulation of the TLR4/NLRP3/GSDMD-mediated pyroptosis pathway, lowering oxidative stress, and improvement of clinical findings. Taking into consideration these findings, it seems that SAZ has the potential to be an effective treatment alternative for the management of arthritis.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113778"},"PeriodicalIF":4.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821814","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 \"Suppression of TLR4 prevents diabetic bone loss by regulating FTO-mediated m⁶A modification\" [Int. Immunopharmacol. 122 (2023) 110510].","authors":"Ximei Shen, Chao Lan, Youfen Lin, Fuyashi Zhang, Yongze Zhang, Mingyun Chen, Sunjie Yan","doi":"10.1016/j.intimp.2024.113723","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113723","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113723"},"PeriodicalIF":4.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817531","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":"Bevacizumab increases cisplatin efficacy by inhibiting epithelial-mesenchymal transition via ALDH1 in cervical carcinoma.","authors":"Na Qu, Zhuo Li, Jing Wei, Yuwei Yang, Yiming Meng, Yuhua Gao","doi":"10.1016/j.intimp.2024.113736","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113736","url":null,"abstract":"<p><p>Cervical carcinoma has the highest incidence among gynaecological cancers in developing countries where the human papillomavirus (HPV) vaccine is not yet widely used. Cancer stem cells (CSCs) are the key factors affecting treatment efficacy and cancer prognosis. Aldehyde dehydrogenase 1 (ALDH1) is a marker of CSCs, and its expression is closely related to chemotherapy resistance in cervical carcinoma. Bevacizumab is the most widely used molecular targeted drug in the management of cervical carcinoma. We designed and performed a series of in vitro and in vivo experiments to investigate the inhibitory effects of these compounds on ALDH1 and the underlying mechanism involved. The results revealed that bevacizumab significantly inhibited epithelial-mesenchymal transition (EMT) in HeLa cervical cancer cells, as indicated by upregulation of E-cadherin and downregulation of N-cadherin and snail. Anoxic pressure was relieved, and tumour vascularization was inhibited in the tumour microenvironment. NOTCH1 plays a critical role in these processes. Through modulating these tumour biological characteristics via ALDH1, bevacizumab increases the sensitivity of cervical carcinoma to cisplatin, suggesting that bevacizumab in combination with standard chemotherapy may represent a new strategy for overcoming drug resistance. Abbreviation: HPV, human papillomavirus; CSCs, cancer stem cells; ALDH1, aldehyde dehydrogenase 1; EMT, epithelial-mesenchymal transition; OD, optical density; qRT-PCR, RNA analysis by quantitative real-time polymerase chain reaction; RIPA, radioimmunoprecipitation assay; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene difluoride; ECL, electrochemiluminescence; NC, negative control; HE, haematoxylin and eosin; IHC, immunohistochemistry; DAB, 3, 3'-diaminobenzidine; IF, immunofluorescence; DAPI, 4,6-diamidino-2-phenylindole; VEGFA, vascular endothelial growth factor A; ROS, oxygen species; DFS, disease-free survival; OS, overall survival; HIF, hypoxia-inducible factor; PDGFs, platelet-derived growth factors; FGFs, fibroblast growth factors; PlGF, placenta growth factor; RTKs, receptor tyrosine kinases.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113736"},"PeriodicalIF":4.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813133","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":"DPP4 promotes an immunoenhancing tumor microenvironment through exhausted CD8+ T cells with activating IL13-IL13RA2 axis in papillary thyroid cancer.","authors":"Ren Jing, Nan Wu, Qian Zhang, Jinlin Liu, Ying Zhao, Shan Zeng, Shaojie Wu, Yang Wu, Shijian Yi","doi":"10.1016/j.intimp.2024.113760","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113760","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid cancer (PTC) is among the most prevalent forms of endocrine malignancy with a rapid rise in incidence rates worldwide; however, the composition and characteristics of its immune microenvironment is poorly understand. Here, this work investigated the precise function of Dipeptidyl peptidase 4 (DPP4) in tumor-infiltrated T cells within PTC by investigating its role in cytokine-mediated signaling pathways.</p><p><strong>Methods: </strong>TCGA and GEO data as well as human PTC specimens confirmed the expression of DPP4 in PTC. The CIBERSORT and TIMER tool were used to analyze the distribution of tumor-infiltrating immune cells in PTC. CD8+ T cells from PTC patient's peripheral blood were cultured and used in a three-dimensional model for direct co-culture with PTC tumors to investigate DPP4 function.</p><p><strong>Results: </strong>Bioinformatic analyses has uncovered a significant upregulation of DPP4, which enhances the survival and migration of PTC cells in vitro. DPP4 upregulation significantly correlated with advanced grades, stages, and poor progression-free survival. DPP4 influences immune function and the exhaustion of CD8+ T cells through the IL13-IL13RA2 axis. The inhibition of DPP4 reduces CD8+ T cell exhaustion and IL13 secretion, while also blocking the IL13-IL13RA2 axis, thereby promoting the mesenchymal-to-epithelial transition of PTC cells.</p><p><strong>Conclusion: </strong>Blocking DPP4 leads to the conversion of exhausted CD8+ T cells with decreased IL13 level, resulting in downregulation of IL13RA2 to promote mesenchymal-to-epithelial transition of PTC cells. This highlights DPP4 as a potential therapeutic target, particularly between CD8+ T cells and PTC cells via IL13-IL13RA2 axis, and represents a novel avenue for combined immunotherapy in PTC.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113760"},"PeriodicalIF":4.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813169","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":"IL-17A exacerbates synovial inflammation in osteoarthritis via activation of endoplasmic reticulum stress.","authors":"Wen Sun, Xueyan Li, Liyuan Zhang, Yuheng Zhang, Yi Shi, Huaqiang Tao, Jing Zhou, Yuefeng Hao, Guangdong Chen, Chengyong Gu, Xing Yang","doi":"10.1016/j.intimp.2024.113733","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113733","url":null,"abstract":"<p><p>The primary clinical manifestations of osteoarthritis (OA) are joint pain and restricted movement capabilities. Synovial inflammation, serving as an initiator of OA progression, intensifies cartilage damage via the generation of various deleterious agents, including pro-inflammatory cytokines and nociceptive mediators. Despite extensive research on modulating synovial inflammation to retard OA progression, the underlying pathophysiological mechanisms of synovial inflammation in OA remain elusive. Interleukin-17A (IL-17A), a pro-inflammatory cytokine released by activated T lymphocytes, is a therapeutic target for numerous inflammatory and autoimmune pathologies. This study investigates the role and mechanism of IL-17A in OA synovial inflammation using both in vivo and in vitro models and examines the impact of the endoplasmic reticulum stress (ERS) inhibitor, 4-Phenylbutyric Acid (4-PBA). Our findings indicate that IL-17A may be implicated in synovial inflammation through ERS and suggest a potential therapeutic direction for mitigating synovial inflammation in OA.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113733"},"PeriodicalIF":4.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813182","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":"CircSugp1 interacts with CPSF6 to modulate intestinal mucosa repair by regulating alternative polyadenylation-mediated shortening of the Wdr89 3'UTR.","authors":"Yu Liao, Ran Li, Hao Zhang, Qi Li, Xiaoqing Xu, Fanze Meng, Yong Sun","doi":"10.1016/j.intimp.2024.113793","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113793","url":null,"abstract":"<p><p>Circular RNAs are a single-stranded non-coding RNAs and play an important role in the development of many diseases. Alternative polyadenylation (APA) regulates the gene 3'UTR length for controlling gene expressions. Although the APA mechanism has been widely studied in the development of diseases, there is no data on its role in the burned intestinal mucosa. We thus herein assessed the role of the circSugp1-initiating APA mechanism in the burned intestinal mucosa. CircSugp1 was downregulated in the intestinal mucosa of burned mice. CircSugp1 promoted proliferation and migration in vitro and in vivo. CircSugp1 promotes the expression of CPSF6; the overexpression of CPSF6 can shorten the gene 3'UTR within the transcript APA range. The promoting effect of circSugp1 on value-added migration was mediated by the APA regulation of the Wdr89 short 3'UTR isoform. CircSugp1 targeted the upregulation of the expression of CPSF6, followed by upregulation of the expression of Wdr89 through APA, promoting the repair of intestinal mucosal damage in burned mice.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113793"},"PeriodicalIF":4.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813147","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":"Preventive effect of MitoQ supplementation and endurance training on glioblastoma and its consequences: TLR4/CREB/ NF-κβ /IL-1β pathway and behaviors.","authors":"Soheil Aminizadeh, Amir Hossein Moslemizadeh, Sara Sheibani, Zahra Sedighi-Khovidak, Zahrasadat Roholamini, Saeideh Jafarinejad-Farsangi, Reza Kheirandish, Vahid Sheibani, Hamideh Bashiri","doi":"10.1016/j.intimp.2024.113756","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113756","url":null,"abstract":"<p><strong>Objective: </strong>The present study investigated the preventive effect of MitoQ supplementation and endurance training (ET) on the TLR4/CREB/ NF-κβ signaling pathway, antioxidant indices, and behaviors in C6-induced glioblastoma (GBM) in rats.</p><p><strong>Methods: </strong>60 male Wistar rats were randomly divided into five groups (n = 12); Sham, Tumor, MitoQ, ET, and MitoQ + ET. Rats in the training groups performed endurance training (5 days per week), and MitoQ at the dose of 250 µM/L daily was administered in drinking water for 8 weeks. At the end of the protocol, all groups except the sham group received 1*10⁶ tumor cells /10 µl culture medium. Two weeks after tumor induction, behavioral tests were performed, and then brain tissue was collected for the histopathology, measurement of antioxidant and inflammatory factors, TLR4, NF-κB proteins, and TLR4, NF-κβ, CREB, IL-1ß, TNF-a, IL-10, Bax, Bcl-2, and Caspase-3 gene expression.</p><p><strong>Results: </strong>The increased level of TLR4 and NF-κβ protein expression in GBM rats decreased in the treatment groups. Gene expression of TLR4, NF-κβ, CREB, TNF-a, IL-10, and Bcl-2 increased in the tumor groups, and treatment groups decreased TLR4, NF-κB, Bcl-2, and CREB. In addition, social behaviors, balance, and memory were impaired in the tumor group, which combination group could improve these behaviors.</p><p><strong>Conclusion: </strong>In sum, the preventive effects of MitoQ as a beneficial immune reactive agent and exercise training in rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, inflammatory factors, and down-regulation of the expression of TLR4.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113756"},"PeriodicalIF":4.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813188","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":"CircFAM64A(3) promoted bladder cancer proliferation and inhibited CD8 + T cell via sponging to miR-149-5p and activated IL-6/JAK/STAT pathway.","authors":"Juntao Zhuang, Ming Zhou, Hao Yu, Rui Zhou, Kexin Bai, Jiancheng Lv, Kai Li, Yidong Cheng, Haiwei Yang, Xiao Yang, Qiang Lu","doi":"10.1016/j.intimp.2024.113762","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113762","url":null,"abstract":"<p><strong>Background: </strong>The significance of circular RNA in tumour biology is increasingly recognized. This study aims to explore the value of circFAM64A(3) in the proliferation and immune evasion of bladder cancer.</p><p><strong>Methods: </strong>Bioinformatics were used to identify the differentially expressed circular RNAs in bladder cancer. Proliferation assay, co-culture assay and flow cytometry assay confirmed the oncogenic and immune-evading characteristics of circFAM64A(3) in bladder cancer in vitro and in vivo. Further, mRNA sequencing, RNA pulldown, and RNA immunoprecipitation were used to confirm the downstream targets and pathways regulated by circFAM64A(3). CUT&TAG assay confirmed HIF-1α promoted the expression of circFAM64A(3) under hypoxic.</p><p><strong>Results: </strong>CircFAM64A(3) was significantly high expression in bladder cancer tissues and related with poor prognosis of bladder cancer patients. CircFAM64A(3) promoted bladder cancer cells proliferation and immune evasion in vitro and in vivo. Mechanistically, circFAM64A(3) acted as a sponge to miR-149-5p and reduced the binding of miR-149-5p to IL-6 3'-UTR. Then, IL-6 activated the JAK/STAT pathway and caused an increase of PD-L1. Under hypoxic environment, HIF-1α bound to the promoter of FAM64A and promoted circFAM64A(3) transcription.</p><p><strong>Conclusion: </strong>HIF-1α/circFAM64A(3)/miR-149-5p/IL-6 axis was an important regulatory pathway in bladder cancer proliferation and immune evasion. CircFAM64A(3) may serve as a novel and potentially valuable biological target.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113762"},"PeriodicalIF":4.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813144","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}