International immunopharmacology最新文献

{"title":"Gentiopicroside ameliorates synovial inflammation and fibrosis in KOA rats by modulating the HMGB1-mediated PI3K/AKT signaling axis","authors":"Yibao Wei ,&nbsp;Zhenyuan Ma ,&nbsp;Zhenhui Li ,&nbsp;Junfeng Kang ,&nbsp;Taiyang Liao ,&nbsp;Lishi Jie ,&nbsp;Deren Liu ,&nbsp;Lei Shi ,&nbsp;Peimin Wang ,&nbsp;Jun Mao ,&nbsp;Peng Wu","doi":"10.1016/j.intimp.2024.113973","DOIUrl":"10.1016/j.intimp.2024.113973","url":null,"abstract":"<div><h3>Background</h3><div>Knee osteoarthritis (KOA) is a degenerative joint disease characterized by synovial inflammation and fibrosis. Gentiopicroside (GPS), one of the main active ingredients of Gentiana macrophylla, is widely used in anti-inflammatory and anti-fibrotic therapies. However, the exact mechanism by which GPS treats synovial inflammation and fibrosis in KOA remains unclear.</div></div><div><h3>Methods</h3><div>Fibroblast-like synoviocytes (FLSs) were stimulated with lipopolysaccharide (LPS) to induce inflammation and fibrosis, and CCK-8 was performed to determine the viability of GPS-treated FLSs, using immunofluorescence to examine the expression of P-PI3K and P-AKT, confocal microscopy was used to identify intracellular HMGB1 translocation. The KOA rat model was established by anterior cruciate ligament transection (ACLT) and subsequently subjected to GPS intervention. Inflammatory cytokines (TNF-α, IL-1β, and IL-6), fibrosis-related indicators (TGF-β, collagen I, TIMP1, and α-SMA), and HMGB1/PI3K/AKT signaling axis-related proteins and gene expression of fibroblast-like synoviocytes and synovial tissues were detected by Western blotting and real-time PCR. The histopathology of the synovium of the rats was assessed using Hematoxylin-eosin (HE), Sirius Red, and Masson staining. Immunohistochemistry was performed to detect the expression of HMGB1, P-PI3K, and P-AKT.</div></div><div><h3>Results</h3><div>The present study revealed that GPS intervention significantly ameliorated inflammation and fibrosis in LPS-stimulated FLSs and KOA rat synovium. Immunofluorescence demonstrated that GPS inhibited the release of HMGB1 from the nucleus. Furthermore, GPS intervention down-regulates the levels of proteins and gene associated with the HMGB1/PI3K/AKT signaling pathway.</div></div><div><h3>Conclusion</h3><div>GPS ameliorated synovial inflammation and fibrosis in KOA rats, which may involve HMGB1-mediated activation of the PI3K/AKT signaling axis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113973"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052221","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":"Regulatory function of endoplasmic reticulum stress in colorectal cancer: Mechanism, facts, and perspectives","authors":"Zihan Liu ,&nbsp;Qiong Liu ,&nbsp;Anqi Zeng ,&nbsp;Linjiang Song","doi":"10.1016/j.intimp.2025.114024","DOIUrl":"10.1016/j.intimp.2025.114024","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is an exceedingly common and profoundly impactful malignancy of the digestive system, posing a grave threat to human health. Endoplasmic reticulum stress (ERS) is an intracellular biological reaction that mobilizes the unfolded protein response (UPR) to tackling dysregulation in protein homeostasis. This process subtly modulates the cell to either restore normal cellular function or steer it towards apoptosis. The high metabolic demands of CRC cells sculpt a rigorous tumor microenvironment (TME), compelling CRC cells to experience ERS. Adaptive responses induced by mild ERS furnish the necessary conditions for the survival of CRC cells, whereas the cell death mechanisms triggered by sustained ERS could be considered a prospective strategy for cancer therapy. Considering the complex regulation of ERS in cancer development, this article offers a comprehensive review of the molecular mechanisms through which ERS influences CRC fate. It provides crucial insights for exploring the role of ERS in the occurrence and progression of CRC, laying a new theoretical foundation for devising precise therapeutic strategies targeting ERS. Furthermore, by synthesizing extensive clinical and preclinical studies, we delve into therapeutic strategies targeting ERS, including the potential of targeting ERS in immunotherapy, the utilization of native compounds, advancements in proteasome inhibitors, and the potential synergies of these strategies with traditional chemotherapy agents and emerging therapeutic approaches.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114024"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052386","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":"Genetic analysis of diagnostic and therapeutic potential for ferroptosis in postoperative sepsis","authors":"Shuaijie Pei ,&nbsp;Jianfeng Liu ,&nbsp;Zhiwei Wang ,&nbsp;Yan Fan ,&nbsp;Shuqi Meng ,&nbsp;Xiaofan Huang ,&nbsp;Yan Cui ,&nbsp;Keliang Xie","doi":"10.1016/j.intimp.2025.114042","DOIUrl":"10.1016/j.intimp.2025.114042","url":null,"abstract":"<div><h3>Background</h3><div>Ferroptosis is a new form of iron-dependent cell death that is closely associated with sepsis. However, few studies have investigated the diagnostic and therapeutic potential for ferroptosis-related genes (FRGs) among postoperative sepsis.</div></div><div><h3>Methods</h3><div>The GSE131761 dataset was used to identify differentially expressed FRGs (DE-FRGs). KEGG and GO analyses were subsequently performed. LASSO and SVM-RFE methods were applied for identifying genetic biomarkers for sepsis. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied for exploring the biological properties of the DEGs. CIBERSORT was applied to analyse immune cell infiltration. DGldb was employed for predicting potential target drugs for the DEGs. Competing endogenous RNA (ceRNA) networks were constructed to analyse the regulatory patterns of the DEGs. The expression of hub genes was validated based on GSE26440 dataset. The bioinformatics analysis was carried out with R software (version 4.1.2). Blood from sepsis patients and healthy controls was collected and the expression of hub genes was experimentally verified by real-time quantitative polymerase chain reaction (RT–qPCR).</div></div><div><h3>Results</h3><div>38 sepsis-associated DE-FRGs were assessed via Gene Expression Omnibus (GEO) and Ferroptosis database (FerrDb), and the gene function analysis showed that they were closely related to inflammatory response and autophagy regulation. Subsequently, SVM-RFE and LASSO methods determined 7 marker genes. GSEA suggested that these marker genes may be involved in regulating several biological pathways. Furthermore, 52 gene-targeted drugs were identified in this study, the vast majority of which were associated with MAPK14. CIBERSORT analysis suggested that SLC38A1, MGST1, and MAPK14 may be involved in immune microenvironment alterations. We revealed the potential complex regulatory relationship by constructing a ceRNA network based on marker genes. Finally, 6 genes were validated in the validation set, with 5 of them further confirmed through RT–qPCR.</div></div><div><h3>Conclusion</h3><div>Seven genes associated with ferroptosis are screened from postoperative sepsis samples. The expression of these genes has high diagnostic validity for sepsis and may serve as potential diagnostic biomarkers. This study gives an entrance point to uncover the underlying mechanisms of sepsis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114042"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964531","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":"Immunotherapy improved the efficacy of TACE or TACE plus MTTs in HCC patients: A meta-analysis","authors":"Yusheng Guo ,&nbsp;Zhenliang Pan ,&nbsp;Xuefeng Kan ,&nbsp;Tianxiang Li ,&nbsp;Bingxin Gong ,&nbsp;Yi Li ,&nbsp;Lian Yang ,&nbsp;Chuansheng Zheng","doi":"10.1016/j.intimp.2024.114006","DOIUrl":"10.1016/j.intimp.2024.114006","url":null,"abstract":"<div><h3>Background</h3><div>Although several studies have compared the efficacy and safety of transarterial chemoembolization (TACE) without immune checkpoint inhibitors (ICIs) and TACE with ICIs, there is still a lack of <em>meta</em>-analysis.</div></div><div><h3>Methods</h3><div>PubMed, Embase, Web of Science, and the Cochrane Library were searched until July 2023 for studies comparing the efficacy and safety of TACE without ICIs (TACE ± molecular targeted therapies [MTTs]) and TACE without ICIs (TACE ± MTTs + ICIs). Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).</div></div><div><h3>Results</h3><div>A total of 20 studies involving 2587 HCC patients were included in the <em>meta</em>-analysis. Eighteen studies including 2116 patients looked at the difference in OS between TACE ± MTTs or TACE ± MTTs + ICIs. Compared with TACE ± MTTs, TACE ± MTTs + ICIs were associated with significantly improved OS (HR, 0.37; 95 % CI, 0.30–0.46). Thirteen studies including 1650 patients investigated the difference in PFS between TACE ± MTTs or TACE ± MTTs + ICIs. The outcome showed that TACE ± MTTs + ICIs were associated with longer PFS (HR, 0.50; 95 % CI, 0.41–0.61, P &lt; 0.001). Eighteen studies including 1971 patients investigated the difference in tumor response (ORR and DCR) between TACE ± MTTs or TACE ± MTTs + ICIs. The outcomes indicated that TACE ± MTTs + ICIs bring higher ORR and DCR compared to TACE ± MTTs (ORR: OR, 2.39; 95 % CI, 1.97–2.89, P &lt; 0.001; DCR: OR, 2.30; 95 % CI, 1.84–2.88). Moreover, to look at the direct impact of ICIs, we investigated the difference in OS, PFS, ORR, DCR, AEs, and severe AEs between TACE + tyrosine kinase inhibitors (TKIs) and TACE + TKIs + ICIs. The results indicated that the addition of ICIs provided longer OS, longer PFS, higher ORR, and higher DCR, but did not bring additional AEs and severe AEs.</div></div><div><h3>Conclusion</h3><div>Immune checkpoint inhibitors improved the efficacy of TACE or TACE plus MTTs and prolonged the survival of patients with hepatocellular carcinoma. Meanwhile, the addition of immune checkpoint inhibitors to the TACE + TKIs did not bring additional adverse events.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114006"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964541","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":"Laminaran potentiates cGAS-STING signaling to enhance antiviral responses","authors":"Lingxiao Xu ,&nbsp;Jiao Lyu ,&nbsp;Zuocheng Qiu ,&nbsp;Qianghui Liu ,&nbsp;Huan Hu ,&nbsp;Longwei Zhao ,&nbsp;Mingyu Pan","doi":"10.1016/j.intimp.2025.114014","DOIUrl":"10.1016/j.intimp.2025.114014","url":null,"abstract":"<div><div>Cyclic GMP–AMP synthase (cGAS)-Stimulator of interferon genes (STING) signaling pathway, an essential element in the innate antiviral immune responses, has emerged as a key component of innate immune system to modulate type I IFNs production and response by recognizing both exogenous and endogenous DNA. Although some cGAS-STING signaling small molecule agonists have been developed, there are few natural polysaccharides reported to activate cGAS-STING signaling for the treatment of infectious diseases. Here, we reported that Laminaran, a low molecular weight β-glucan storage polysaccharide present in brown algae, potentiates cGAS-STING signaling to promote type I IFNs production and antiviral response. Laminaran enhanced cGAS-STING signaling mediated type I IFNs production and response both in human and murine cells upon HSV-1 infection or DNA mimics stimulation. Importantly, we found that Laminaran markedly inhibited Herpes simplex virus-1 (HSV-1) induced death and inflammatory responses and increased the induction of type I IFNs in C57BL/6J mice. Mechanistically, we found Laminaran inhibited autophagy and suppressed STING autophagic degradation to positively regulate cGAS-STING signaling response. Taken together, we uncovered the function of Laminaran in DNA triggered innate immunity by enhancing cGAS-STING signaling response. Laminaran might be a potential therapeutic candidate for viral infectious diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114014"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964544","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":"SFAs facilitates ceramide’s de novo synthesis via TLR4 and intensifies hepatocyte lipotoxicity","authors":"Yuchao Zou ,&nbsp;Lulu Tian ,&nbsp;Liuhua Pei ,&nbsp;Jie Hao ,&nbsp;Tianhang Chen ,&nbsp;Jiayu Qi ,&nbsp;Jiannan Qiu ,&nbsp;Yinuo Xu ,&nbsp;Xiaokai Hu ,&nbsp;Lin Chen ,&nbsp;Xiaobing Dou","doi":"10.1016/j.intimp.2025.114020","DOIUrl":"10.1016/j.intimp.2025.114020","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic steatohepatitis (NASH), an advanced manifestation of non-alcoholic fatty liver disease (NAFLD), is characterized by hepatocyte injury, inflammation, and fibrosis. Saturated fatty acids (SFAs) have emerged as key contributors to hepatocyte lipotoxicity and disease progression. Toll-like receptor 4 (TLR4) acts as a sentinel for diverse ligands, including lipopolysaccharide (LPS) and endogenous molecules like palmitic acid (PA)-induced ceramide (CER) accumulation, promoting hepatocyte demise. However, the intricate mechanisms underlying TLR4′s modulation of ceramide metabolism and their concerted effect on SFA-mediated hepatotoxicity remain elusive.</div></div><div><h3>Methods</h3><div>A NASH mouse model with liver-specific TLR4 knockdown was established through palm oil feeding and AAV2/8 tail vein injection. Histological and biochemical assessments were conducted to evaluate the mice’s condition and liver damage extent. Liquid chromatography-mass spectrometry (LC-MS) was employed to quantify ceramide levels in liver tissues, offering insights into NASH mechanisms.</div></div><div><h3>Results</h3><div>The PO-fed model exhibited elevated serum ALT, AST, and liver TG levels, enhancing lipid accumulation and hepatocellular damage. TLR4 knock-down reduced liver mass and the liver-to-body weight ratio, signifying a decreased hepatic burden. Histopathological evaluations revealed substantial improvement in hepatic steatosis in TLR4-silenced PO-fed mice, with diminished lipid droplets and inflammatory infiltrates. LC-MS analysis showed a marked decrease in long-chain ceramides (C14, C16, C20) in TLR4-knockdown PO-fed mice. Furthermore, expression of MyD88, SPTLC1, SPTLC2, and inflammatory markers IL-1β, IL-6, TNF-α were significantly attenuated.</div></div><div><h3>Conclusion</h3><div>SFAs activate the TLR4 signaling pathway via MyD88, fostering ceramide <em>de novo</em> synthesis, which exacerbates hepatocyte lipotoxicity and accelerates NASH progression.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114020"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964555","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":"Soluble CD72 concurrently impairs T cell functions while enhances inflammatory response in sepsis","authors":"Jing Yang ,&nbsp;Chengyong Ma ,&nbsp;Zhongxue Feng ,&nbsp;Fei Xiao ,&nbsp;Yan Kang ,&nbsp;Wei Zhang ,&nbsp;Xuelian Liao","doi":"10.1016/j.intimp.2024.113981","DOIUrl":"10.1016/j.intimp.2024.113981","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is defined as multi-organ dysfunction caused by dysregulated host response to infection. This dysregulated host response includes enhanced inflammatory responses and suppressed adaptive immunity, but the molecular mechanisms behind it have not yet been elucidated. CD72, a type II transmembrane protein that is primarily expressed in B cells, was found to play an immunomodulatory role in the immune system and was associated with mortality in patients with sepsis. However, whether CD72 affects the pathogenesis of sepsis by influencing the immune response remains unclear.</div></div><div><h3>Methods</h3><div>We first collected peripheral blood from 40 healthy volunteers and 57 septic patients and analyzed the mRNA levels of CD72 and the expression of its soluble form sCD72 using Realtime-PCR and ELISA. We then employed the CRISPR/Cas9 system to generate CD72 knockout mice (CD72-KO) and established a cecal ligation and puncture (CLP) model to analyze the effects of CD72 gene deletion on the survival, organ injury and immune response of septic mice by Kaplan-Meier survival analysis, pathological sections and flow cytometry. We also observe the effects of excess sCD72 on survival and immune response in sepsis by injecting recombinant CD72 protein into mice. Finally, the mechanism of sCD72 affecting sepsis immunity was analyzed by fluorescence staining, confocal microscopy and flow cytometry.</div></div><div><h3>Results</h3><div>We found that when sepsis occurs, the levels of CD72 mRNA and cell surface CD72 in immune cells decrease, while the level of soluble sCD72 in the blood increases significantly. Excessive sCD72 increased sepsis mortality in a dose-dependent manner, which can bind to CD100 on the surface of T cells and enter the cytoplasm, leading to impaired T cell functions, including a decrease in CD4⁺IFN-γ⁺, CD8⁺Perforin⁺, CD8⁺GZMB⁺, and CD8⁺FASL⁺ population and an increase in inflammatory CD4⁺TNF-α⁺ population, thereby suppressing adaptive immunity while enhancing inflammatory response.</div></div><div><h3>Conclusion</h3><div>The immunosuppression of sepsis has been recognized, but the underlying mechanism has not been fully elucidated. Our study identified for the first time that sCD72 is an important mediator that cause adaptive immunosuppression during sepsis, which leads to T cell suppression by competitively binding to CD100 on the surface of T cells. Our study provides novel insights in our understanding of sepsis-related immunosuppression and may provide translational opportunities for the design of new diagnostic biomarkers and therapeutic targets for sepsis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113981"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964560","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":"Cyclopamine inhibits corneal neovascularization and fibrosis by alleviating inflammatory macrophage recruitment and endothelial cell activation","authors":"Xue-Jiao Chang ,&nbsp;Xiao-Xiao Guo ,&nbsp;Jing Li ,&nbsp;Qi Pu ,&nbsp;Xin-Yu Li","doi":"10.1016/j.intimp.2025.114025","DOIUrl":"10.1016/j.intimp.2025.114025","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore the function of cyclopamine in corneal neovascularization and subsequent fibrosis after cornea alkali-burn injury.</div></div><div><h3>Methods</h3><div>In vivo, mice cornea were injured by NaOH, and then treated with cyclopamine, clodronate liposomes (CLO-LPS), and vehicle of cyclopamine separately by subconjunctival injections. Clinical features were observed and pathological characteristics were examined. In vitro, M1 macrophages (M1φ) and human umbilical vein endothelial cells (HUVECs) were co-cultured, and the abilities of proliferation, migration, and tube formation of HUVECs were detected under different interventions of M1φ.</div></div><div><h3>Results</h3><div>Alkali-burn injury induced massive angiogenesis and decreased transparency of the cornea, along with numerous macrophages infiltration and Shh protein expression in the cornea. However, corneal neovascularization, macrophage infiltration, and Shh expression could suppressed by cyclopamine and CLO-LPS significantly. In addition, treatment with cyclopamine also reduced the expression of inflammatory factors (TNF-α, IL-6) and fibrosis factors (VIM, α-SMA). In vitro, M1φ promotes migration and tube formation of HUVECs by secreting Shh protein, which could be inhibited by cyclopamine.</div></div><div><h3>Conclusion</h3><div>Cyclopamine could suppress inflammation and angiogenesis of alkali-burned cornea, as well as subsequent fibrosis. The study reveals that cyclopamine suppresses corneal neovascularization in a dual mechanism of inhibiting macrophage infiltration and suppressing Shh signaling.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 114025"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970784","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":"RBM47 as a potential therapeutic target for thyroid-associated ophthalmopathy","authors":"Ru Zhu ,&nbsp;Fei Chen ,&nbsp;Bo-Wen Wang ,&nbsp;Ying Jin ,&nbsp;Jun-Jie Yang ,&nbsp;Bing-Jie Shi ,&nbsp;Yu-Ting Chen ,&nbsp;Fa-Gang Jiang ,&nbsp;Xing-Hua Wang","doi":"10.1016/j.intimp.2024.113955","DOIUrl":"10.1016/j.intimp.2024.113955","url":null,"abstract":"<div><div>RNA-binding motif 47 (RBM47) is a recently identified RNA-binding protein involved in early vertebrate development, immune homeostasis, and cancer development. This study examined the biological functions of RBM47 in thyroid-associated ophthalmopathy (TAO). Orbital fibroblasts (OFs) were obtained from the control (n = 6) and TAO groups (n = 6). Protein and gene expression in the obtained samples were investigated using immunohistochemistry, western blotting (WB), and RT-PCR. OFs with <em>RBM47</em> knockdown were established using small interfering RNA. Subsequently, Oil Red O staining, WB, and RT-PCR were performed to assess adipogenesis in the OFs. The IL-1β-induced expression of proinflammatory molecules and hyaluronan (HA) was determined using enzyme-linked immunosorbent assay and RT-PCR. Moreover, TGF-β-induced fibrosis was evaluated using scratch assays, RT-PCR, and WB. RBM47 expression was markedly increased in orbital tissues and OFs obtained from individuals with TAO. <em>RBM47</em> knockdown decreased adipogenesis and fibrosis in OFs, and downregulated the levels of insulin-like growth factor 1 receptor (IGF-1R), proinflammatory molecules, and HA. Furthermore, low <em>RBM47</em> expression downregulated IGF-1R, which subsequently inhibited adipocyte differentiation by decreasing extracellular signal-regulated kinase signalling. These findings indicate that RBM47 may be involved in the regulation of adipogenesis, inflammation, HA production, and fibrosis, highlighting its potential of RBM47 as a therapeutic target for TAO.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113955"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921690","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":"Deletion of BMP4 impairs trophoblast function and decidual macrophage polarization via autophagy leading to recurrent spontaneous abortion.","authors":"Lujia Tang, Fangfang Dai, Yuwei Zhang, Ruiqi Wang, Wei Tan, Ran Gu, Liping Chen, Linlin Wang, Hua Liu, Yanxiang Cheng, Liangbin Xia","doi":"10.1016/j.intimp.2025.114015","DOIUrl":"10.1016/j.intimp.2025.114015","url":null,"abstract":"<p><p>Bone morphogenetic protein 4 (BMP4) is widely involved in the regulation of cell proliferation and differentiation, but its role in Recurrent Spontaneous Abortion (RSA) remains unclear. RSA is a disease that affects roughly 1-2% of partner pairs, but its pathogenesis is still unclear. In recent years, many studies have focused on the role of decidual macrophages in RSA. In this study, we found decreased expression levels of BMP4 in villous tissues of RSA patients and found that low expression of RUNX2 leads to down-regulation of BMP4, which impairs trophoblast function. More importantly, we found in both co-culture system and human recombinant BMP4 protein models that BMP4 overexpression polarizes THP-1-derived macrophages toward M2, and down-regulation of BMP4 leads to macrophage polarization toward M1. Mechanically, we found that BMP4 promotes macrophage polarization via regulating autophagy level. The recovery experiment was further confirmed that 3-MA (autophagy inhibitor) inhibit THP-1-derived macrophage polarization toward M2 induced by BMP4 overexpression and exogenous addition of rBMP4, and rapamycin (autophagy agonists) inhibit macrophages polarization toward M1 from down-regulation of BMP4. Our study further reveals the mechanism of maternal-fetal interface cell interactions in RSA, which can help in the diagnosis and treatment of RSA.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"114015"},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978333","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}