Molecular immunology最新文献

{"title":"LncRNA XIST inhibits mitophagy and increases mitochondrial dysfunction by promoting BNIP3 promoter methylation to facilitate the progression of KBD","authors":"Ruoxi Liu ,&nbsp;Yi Xiao ,&nbsp;Sihua Huang ,&nbsp;Hao Wu ,&nbsp;Jun Dong ,&nbsp;Sixiang Zeng ,&nbsp;Yongwei Li ,&nbsp;Jintao Ye ,&nbsp;Wei Wu ,&nbsp;Mengxin Wang ,&nbsp;Sanpeng Zhang ,&nbsp;Zhaoxing Lin ,&nbsp;Huanjin Song","doi":"10.1016/j.molimm.2025.03.016","DOIUrl":"10.1016/j.molimm.2025.03.016","url":null,"abstract":"<div><div>The primary mechanisms underlying cartilage destruction in Kashin-Beck disease (KBD) involve excessive chondrocyte death and extracellular matrix (ECM) degradation. While long non-coding RNA XIST (lncRNA XIST) has been implicated in promoting chondrocyte injury in osteoarthritis (OA), its role in KBD-related chondrocyte injury remains poorly understood. In this study, joint tissues were collected from four healthy and four KBD-affected children, as well as five healthy and five KBD-affected adults, to assess the expression of lncRNA XIST. The results revealed a significant upregulation of lncRNA XIST in the cartilage tissues of KBD patients. To model KBD-induced chondrocyte damage in vitro, hypertrophic ATDC5 cells were exposed to 10 ng/ml T-2 toxin for 24 hours, which resulted in increased lncRNA XIST expression. Silencing lncRNA XIST was found to mitigate T-2 toxin-induced ECM degradation and chondrocyte apoptosis by alleviating defects in mitochondrial autophagy and dysfunction. Mechanistically, lncRNA XIST promoted the methylation of the BNIP3 promoter by recruiting DNA methyltransferases (DNMTs) to the BNIP3 promoter region, thereby suppressing BNIP3-mediated mitophagy and exacerbating mitochondrial dysfunction. To establish a KBD rat model, rats were fed a low-selenium diet supplemented with T-2 toxin for four weeks. Knockdown of lncRNA XIST in these rats attenuated articular cartilage damage and apoptosis, while enhancing collagen II expression. In conclusion, lncRNA XIST accelerates KBD progression by inhibiting mitophagy and promoting mitochondrial dysfunction through increased BNIP3 promoter methylation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 62-75"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-770 promotes polarization of macrophages and hemorrhoids by suppressing RYBP expression and monoubiquitination of histone H2A on Lys119 modification","authors":"Haikun Zhou ,&nbsp;Te Liu ,&nbsp;Shenglan Zhong ,&nbsp;Wei Yang","doi":"10.1016/j.molimm.2025.03.017","DOIUrl":"10.1016/j.molimm.2025.03.017","url":null,"abstract":"<div><div>Hemorrhoid disease (HD) is a common proctological condition whose onset is associated with an abnormal inflammatory microenvironment; however, the underlying mechanisms remain unclear. In this study, pathological examination revealed a significant increase in MΦ1 macrophages in the hemorrhoidal tissue of patients with HD, along with elevated levels of inflammatory factors. qPCR results demonstrated that the expression of several members of the DLK1-DIO3 microRNA cluster, particularly miR-770, was significantly higher in the hemorrhoid tissue of patients with HD than in that of the control group. Luciferase reporter assays confirmed that RYBP is a target gene negatively regulated by miR-770. Additionally, qPCR and western blot analyses indicated that overexpression of miR-770 significantly downregulated the expression of PRC1 family genes and RYBP in THP-1 cells, while concurrently upregulating the expression of inflammatory factors such as NFKB, IL1b, IL4, TNF, and IFNG. The overexpression of miR-770 significantly induced the polarization of THP-1 cells toward MΦ1. Mechanistic studies using ChIP-seq revealed that miR-770 overexpression significantly reduced the number of gene promoters in MΦ1 cells that bind to histone H2AK119-Ub sites. Furthermore, the number of enriched DNA fragments from genes that bind to the + 1 transcription start site of histone H2AK119-Ub, such as NFKB1, IL1B, and TNF, was significantly lower than that observed in the control group. Therefore, we confirmed that miR-770, a genomic imprinted member of the DLK1-DIO3 region, negatively regulated the expression of the PRC1 family member RYBP, reduced the level of ubiquitination modification at histone H2AK119-Ub, and promoted the transcriptional activation of pro-inflammatory genes. This ultimately leads to MΦ1 polarization and the release of inflammatory factors, elucidating the epigenetic mechanisms underlying the occurrence of hemorrhoids.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 41-53"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK cellular derived nanovesicles in tumor immunity","authors":"Dingru Li ,&nbsp;Yixin Shi ,&nbsp;Sifei Yu ,&nbsp;Beiying Zhang ,&nbsp;Ziyi Huang ,&nbsp;Fei Ling ,&nbsp;Xiaofan Mao ,&nbsp;Yuhua Deng ,&nbsp;Mengyun Cai ,&nbsp;Wei Luo","doi":"10.1016/j.molimm.2025.03.018","DOIUrl":"10.1016/j.molimm.2025.03.018","url":null,"abstract":"<div><div>Natural Killer (NK) cells are a vital element of the innate immune system, and NK cell-based therapies have demonstrated efficacy against various malignancies. However, targeting solid tumors has been challenging due to the low infiltration of NK cells into tumors and the effective evasion strategies employed by tumors. Recent studies have shown that NK cell derived nanovesicles (NK-NV) can not only replicate the functions of NK cells but also offer more advantages in clinical applications. They are capable of transporting various cellular components such as proteins, nucleic acids, and lipids across distances, thereby facilitating intercellular communication among various cells within the tumor microenvironment (TME). With the progress in nanomedical technology, these vesicles can be engineered to carry a range of functional elements and therapeutic agents to enhance their antitumoral capabilities. In this review, we summarize the current available literature on NK-NVs, discuss their potential biological functions and the role of non-coding RNAs (ncRNAs), and explore their application in the treatment of solid tumors.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 54-61"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-tumor effectiveness of a novel bispecific antibody that blocks both PD-L1 and LAG-3","authors":"Chenxing Zhang ,&nbsp;Jiaxin Liu ,&nbsp;Minglv Sun ,&nbsp;Tiejun Gu ,&nbsp;Xiangyu Meng ,&nbsp;Shidong Zhu ,&nbsp;Youfeng Zhang ,&nbsp;Linlin Wang ,&nbsp;Yan Chen ,&nbsp;Daguang Zhang ,&nbsp;Yongge Wu","doi":"10.1016/j.molimm.2025.03.015","DOIUrl":"10.1016/j.molimm.2025.03.015","url":null,"abstract":"<div><div>Over the past few years, substantial progress with promising outcomes were achieved for the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in immunotherapy. However, several issues still limit their effectiveness for anti-cancer therapy. Therefore, we designed a bispecific antibody (referred to as Ba-PL) against PD-L1 and T cell immune checkpoint lymphocyte activation gene-3 (LAG-3), in an attempt to block both targets to further improve immune efficacy against solid tumors. A bispecific T cell engager structure was used to connect the variable regions of the PD-L1 and LAG-3 antibodies in series. The antibody was prepared using a prokaryotic expression system, and its molecular and cellular-level affinity was assessed in vitro. Furthermore, we preliminarily evaluated its anti-tumor effects in mice. Collectively, the antibody prepared using the prokaryotic expression system had preferable tumor cell-targeting ability and blocked the interaction of PD-1 and LAG-3 with their ligands. Further, the results of the animal experiments demonstrated that the Ba-PL exerted a better anti-tumor effect in 4T1 and H22 tumor-bearing mice. Overall, our study suggests that this strategy has therapeutic potential for liver hepatocellular and breast invasive carcinoma.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 30-40"},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marvelon suppresses MC38 tumor growth and promotes anti-tumor immunity","authors":"Fandi Kong ,&nbsp;Yongyan Chen ,&nbsp;Dantong Liu,&nbsp;Hongying Gao,&nbsp;Qiaoru Yi,&nbsp;Mengjuan Zhang,&nbsp;Dan Li","doi":"10.1016/j.molimm.2025.03.011","DOIUrl":"10.1016/j.molimm.2025.03.011","url":null,"abstract":"<div><div>Colorectal cancer is a prevalent and deadly malignancy globally, posing an important challenge due to its heterogeneity and treatment resistance. Although oral contraceptives have been shown to reduce the incidence of colorectal cancer, their impact on the anti-tumor effect of CD8⁺ T cells remains unclear. Here we show that the contraceptive Marvelon plays an important role in anti-MC38 tumor immunity. The contraceptive Marvelon significantly inhibits MC38 tumor growth in vivo. Marvelon treatment promotes IFN-γ expression in CD8⁺ tumor infiltrating lymphocytes, but shows dispensable impact on their exhausted profile. By further investigating the effects of Marvelon’s primary components, Ethinylestradiol and Desogestrel, we reveal that Ethinylestradiol enhances IFN-γ production in Type 1 Cytotoxic T (Tc1) cells and significantly inhibits the viability of MC38 tumor cells, whereas Desogestrel exhibits minimal effects. This study not only redefines the role of oral contraceptives but also provides valuable insights for the development of novel immunotherapeutic strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 20-29"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobiomodulation regulates inflammation and autophagy in spinal cord injury through NLRP3/Caspase-1/IL-1β pathway by targeting TLR2","authors":"Xiaoshuang Zuo ,&nbsp;Cheng Ju ,&nbsp;Zhihao Zhang ,&nbsp;Xinghui Wei ,&nbsp;Yangguang Ma ,&nbsp;Zhiwen Song ,&nbsp;Jiawei Zhang ,&nbsp;Liang Luo ,&nbsp;Zhijie Zhu ,&nbsp;Zhe Wang ,&nbsp;Xueyu Hu","doi":"10.1016/j.molimm.2025.03.014","DOIUrl":"10.1016/j.molimm.2025.03.014","url":null,"abstract":"<div><div>After spinal cord injury (SCI), peripherally derived macrophages infiltrated the injury area to exert inflammatory effects, causing barriers to the repair of spinal cord injury. Our previous study confirmed that photobiomodulation (PBM) could promote the motor function recovery and inhibit the secretion of inflammatory cytokines after SCI, moreover, PBM also has a role in promoting autophagy, but the mechanism is not clear. Therefore, we aimed to investigate whether PBM promotes autophagy by regulating the inflammatory response of macrophages, which in turn regulates functional repair after SCI. Male C57/BL6 mice were used to prepare a model of clamped spinal cord injury, and PBM irradiation was performed for 28 consecutive days, which showed that motor function of the mice was improved. We observed that autophagy proteins (LC3, Beclin-1 and P62) were inhibited and inflammasome-related proteins (NLRP3, Caspase-1 and IL-1β) expression was significantly enhanced in SCI mice. We analyzed the RNA sequencing (RNA-seq) of SCI, SCI+PBM treated mice in combination with autophagy database. The results showed 25 differentially expressed genes (DEGs). Protein-protein interaction (PPI) network and Hub gene analysis revealed TLR2 as a key molecule in the regulation of autophagy levels by PBM after SCI. We performed preliminary analysis in macrophages cultured in <em>vitro</em> and observed that PBM suppressed the expression of TLR2 and inflammasome-related proteins in M1-type macrophages and promoted the expression of autophagy proteins. Subsequently, we used an agonist of TLR2 (CU-T12–9) to up regulate TLR2 expression and observed that macrophage autophagy was inhibited and inflammatory response was enhanced. After PBM irradiation, the effect of CU-T12–9 was counteracted. Taken together, PBM promotes autophagy and attenuates the inflammatory response by regulating TLR2, a key molecule of autophagy in spinal cord injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brucella lipopolysaccharide deficiency with lipid A induces robust T cells immune response","authors":"Jian-Dong Zhang,&nbsp;Qun Wang,&nbsp;Hong-Xia Hu,&nbsp;Kai-Xuan Guo,&nbsp;Chao-Yue Guo,&nbsp;Huan-Chun Chen,&nbsp;Zheng-Fei Liu","doi":"10.1016/j.molimm.2025.03.006","DOIUrl":"10.1016/j.molimm.2025.03.006","url":null,"abstract":"<div><div><em>Brucella</em>, an opportunistic intracellular parasitic bacterium, is classified as a Gram-negative organism. Lipopolysaccharide (LPS), as primary virulence factor of <em>Brucella</em>, includes lipid A, O-antigen, and core polysaccharide, with lipid A being the principal component. The atypical structure of <em>Brucella</em> LPS, noted for its very-long-chain fatty acids, may suppress the host immune response, thus facilitating chronic disease development. The mechanism by which these chains induce immunosuppression remains poorly understood.This study aimed to investigate these chains through deletion of the <em>BacA</em> gene. We extracted LPS to stimulate Bone Marrow-Derived Dendritic Cells (BMDCs) <em>in vitro</em> and co-cultured them with T cells to induce proliferation and differentiation. The <em>in vivo</em> immune response to LPS was evaluated through routine blood tests, CD4 and CD8 assays, and lymphocyte stimulation indices. Our findings demonstrate that wild-type LPS from <em>B. melitensis</em> (Bm-WT) does not elicit an immunostimulatory response <em>in vitro</em>; rather, it promotes immune suppression <em>in vivo</em>. In contrast, LPS derived from <em>B. melitensis</em> with a mutated <em>BacA</em> gene (Bm-Δ<em>BacA</em>) disrupts the immune suppression and encourages the production of inflammatory factors. These findings underscore the crucial role of modifying lipid A through molecular biology techniques to advance bacterial vaccines and adjuvants.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 11-19"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypericin impedes M2 macrophage polarization and protects against Hepatocellular carcinoma","authors":"Xinru Wen ,&nbsp;Xianling Wang ,&nbsp;Qing Yao ,&nbsp;Simin Chen ,&nbsp;Chengwei Li ,&nbsp;Congyang Zheng ,&nbsp;Ang Huang ,&nbsp;Xiaoyan Zhan ,&nbsp;Zhaofang Bai ,&nbsp;Xiaohe Xiao","doi":"10.1016/j.molimm.2025.03.012","DOIUrl":"10.1016/j.molimm.2025.03.012","url":null,"abstract":"<div><h3>Background</h3><div>There has been increasing evidence that M2 polarization, which is essential for tumor growth, is present in most tumor-associated macrophages. Hypericin is the major component of the Traditional Chinese Medicine <em>Hypericum perforatum</em>. Hypericin exhibits antitumor activities, but its regulation on M2 macrophage polarization and the protective against Hepatocellular carcinoma (HCC) remains unknown.</div></div><div><h3>Methods</h3><div>IL-4 was used to induce bone marrow-derived macrophages (BMDMs) to differentiate into M2 macrophages, the effect of hypericin on M2 polarization of BMDMs was investigated, mRNA level of M2-related genes was determined using RT-qPCR and flow cytometry. Furthermore, the effect of culture medium of M2 macrophage (M2-CM) pretreated with hypericin or not on the proliferation, migration, and invasion of Hepa1–6 cells was studied. To investigate the mechanism, the PI3K/AKT signaling pathway, which is critical in macrophage polarization was tested. A mouse model of HCC was established by subcutaneous implantation of H22 cells, the impact of Hyp on tumor growth and M2 macrophage polarization in tumor tissues was identified.</div></div><div><h3>Results</h3><div>In the present study, we found that Hyp significantly inhibited M2 polarization of macrophages, as indicated by decreased expression of CD206 and M2-related markers, moreover, Hyp suppressed the M2-CM-induced proliferation, invasion and migration of Hepa1–6 cells. Hyp manifested an inhibitory effect on the PI3K/AKT signaling pathway during the differentiation of M2 macrophages. In vivo experiments showed that Hyp greatly suppressed tumor growth and reduced M2 macrophage polarization in tumor tissues.</div></div><div><h3>Conclusion</h3><div>Hyp impedes the growth, proliferation, invasion and migration of HCC by inhibiting M2 macrophages polarization via the PI3K/AKT signaling pathway, our data demonstrate that hypericin may be a promising candidate for HCC treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 160-168"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuritin-specific antibody impedes the Treg-mediated suppression of anti-tumor immunity and enhances response to anti-PD1","authors":"Kaimin Zhang ,&nbsp;Taowen Zhao ,&nbsp;Fraooq Riaz ,&nbsp;Yikui Li ,&nbsp;Ping Wei ,&nbsp;Xiang Fang ,&nbsp;Zhiyi Zhou ,&nbsp;Wei Kou ,&nbsp;Fan Pan","doi":"10.1016/j.molimm.2025.03.013","DOIUrl":"10.1016/j.molimm.2025.03.013","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) and effector T cells play critical roles in tumor immunity, with Tregs suppressing immune responses and contributing to an immunosuppressive tumor microenvironment (TME). Neuritin-1 (Nrn), a neuropeptide, has been identified to enhance Treg expansion. However, its role in T cell biology and tumor development remains unclear. We demonstrated that Nrn is highly expressed in the in-vitro-induced Tregs (iTregs). Functionally, Nrn promoted iTreg differentiation in a dose-dependent manner, while Nrn deletion or anti-Nrn antibody treatment significantly inhibited iTreg differentiation. Additionally, Nrn suppressed IL-2 transcription and secretion in T cells, impairing T cell activation and pro-inflammatory cytokine production. Treg-specific Nrn knockout mice exhibited reduced B16 melanoma tumor growth, decreased Treg infiltration, and increased effector T cell infiltration. Conversely, overexpression of Nrn accelerated B16 melanoma tumor progression by enhancing Treg-mediated suppression. Importantly, we developed the first anti-Nrn antibody, which effectively reduced tumour growth, decreased Treg infiltration, and enhanced effector T-cell activity. Importantly, anti-Nrn synergistically worked with anti-PD1 and improved the anti-PD1 response by reducing Tregs and increasing effector function in tumor-infiltrated T cells, resulting in enhanced tumor regression. Our findings identify Nrn as a critical regulator of Treg differentiation and effector T cell suppression, contributing to tumor progression. Targeting Nrn alone or combined with anti-PD1 therapy represents a promising strategy to enhance anti-tumor immunity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 148-159"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound C1 reduced inflammation and activated autophagy in alveolar macrophages in mice","authors":"Qi Sheng ,&nbsp;Jie Zhao ,&nbsp;Shujun Chen ,&nbsp;Jingmin Zeng ,&nbsp;Shaogui Wang ,&nbsp;Jinping Wang","doi":"10.1016/j.molimm.2025.03.010","DOIUrl":"10.1016/j.molimm.2025.03.010","url":null,"abstract":"<div><div>The purpose of this study was to investigate the therapeutic effect of Compound C1 (Comp-C1) on lipopolysaccharide (LPS) -mediated sepsis acute lung injury (SALI) in vitro alveolar macrophage model and its regulatory mechanism. In vitro cultured mouse alveolar macrophages (MH-S) were treated with LPS. The expression and localization of transcription factor EB (TFEB) after LPS stimulation were detected. Then the cells were treated with LPS (1 μg/mL) and Comp-C1 (1 μM) for 24 h. RT-qPCR and Western Blot were used to detect the mRNA expression of inflammatory factors. Western blot was used to detect the expression of TFEB, lysosome-associated membrane protein 1 (LAMP1), P62 and microtubule-associated protein 1 light chain 3B (LC3B). TFEB-EGFP-Hela and mCherry-EGFP-LC3-Hela cells were used to detect the changes of TFEB nuclear expression and intracellular autophagic flux after Comp-C1 administration by immunofluorescence. The results showed that the expression of inflammatory factors was the highest after 1 μg / mL LPS stimulation for 24 hours. At the same time, the expression of TFEB gene and protein decreased after LPS stimulation, and the content of TFEB in cytoplasm and nucleus decreased by separating cytoplasmic and nuclear proteins. The content of LAMP1 decreased, and the expression of autophagy-related proteins reflected the inhibition of autophagy. After treatment with Comp-C1, the inflammatory factors were significantly decreased, the expression of TFEB and LAMP1 was significantly increased, and the expression of autophagy genes in the cells was restored. The up-regulation of TFEB nuclear expression after Comp-C1 administration was determined by TFEB-EGFP-Hela cells, and the recovery of autophagy flux and alveolar macrophage function after Comp-C1 administration was determined by mCherry-EGFP-LC3-Hela cells. Therefore, Comp-C1 can alleviate LPS-induced MH-S autophagy dysfunction and reduce inflammatory response by up-regulating TFEB in mouse alveolar macrophages, suggesting that Comp-C1 can be used as a potential drug for the treatment of SALI</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 139-147"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}