Molecular immunology最新文献

{"title":"Paeoniflorin as a potential agent for urticaria treatment: Suppressing mast cell degranulation through HMGB1/TLR4/NF-κB signaling inhibition","authors":"Xurui Wang ,&nbsp;Anjing Chen ,&nbsp;Yaobin Pang ,&nbsp;Changcheng Hou ,&nbsp;Yueyue Wang ,&nbsp;E. Liu ,&nbsp;Yijia Zhao ,&nbsp;Jing Guo ,&nbsp;Mingyue Li","doi":"10.1016/j.molimm.2025.04.013","DOIUrl":"10.1016/j.molimm.2025.04.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Paeoniflorin (PF) has strong immunomodulatory effects and has been widely used in the treatment of many diseases, but its mechanism of action in urticaria is not clear. The aim of this experiment was to investigate the role and mechanism of paeoniflorin in improving mast cell degranulation in urticaria.</div></div><div><h3>Methods</h3><div>The mouse model of urticaria was replicated by ovalbumin+ aluminum hydroxide method, and the mast cell degranulation model was induced by anti-DNP IgE+ Dinitrophenyl- Bovine Serum Albumin (DNP-BSA), and the mice and cells were intervened by different doses of PF. The histopathological changes of the dorsal skin were observed using hematoxylin-eosin (HE) staining, the infiltration of mast cells was observed by Toluidine blue staining, the expression of mast cell tryptase (MCT) was examined by Immunohistochemical staining, the cell viability was detected by CCK8 assay, and Rhod-2/AM flow cytometry assay to determine calcium ion content, enzyme-linked immunosorbent assay (ELISA) detected mast cell degranulation-associated factors, and Western blot analyzed HMGB1/TLR4/NF-κB signaling factors.</div></div><div><h3>Results</h3><div>PF reduced the number of scratches in mice, ameliorated histopathological damage in dorsal skin, decreased mast cell degranulation rate, reduced the levels of Ca^2 +, MCT, β-HEX, HIS, MCP-1, TNF-α, and IL-13, and inhibited the expression of HMGB1, TLR4, MyD88, NF-κB p65 (Nucleus), and p-IκBα. Moreover, Rec-HMGB1 reversed the effect of PF.</div></div><div><h3>Conclusion</h3><div>PF mitigates urticarial mast cell degranulation through the inhibition of the HMGB1/TLR4/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for the treatment of urticaria.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 33-43"},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899462","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":"Smart materials in pharmacological drug development: Neutrophils and its constituents for drug delivery and consequent antitumor effects","authors":"Shengjie Cai ,&nbsp;Xuehan Wei ,&nbsp;Qian Li ,&nbsp;Ziyu Jiang ,&nbsp;Lingchang Li","doi":"10.1016/j.molimm.2025.04.010","DOIUrl":"10.1016/j.molimm.2025.04.010","url":null,"abstract":"<div><div><strong>N</strong>eutrophil-based drug delivery systems for targeted therapy of cancer have been studied widely in the recent past. Chemotactic cytokines including colony-stimulating factors (CSFs) recruit various immune cells including the neutrophils to the tumor microenvironment (TME) leading to enhanced metastasis. These cytokines can be targeted effectively by immunotherapeutic agents such as checkpoint inhibitors and mAbs that can lead to systemic toxicity. To minimize the systemic adverse effects, camouflaged nanoparticles can be used significantly as alternative therapeutic agents. The neutrophil-interacting NPs and neutrophil membrane coated NPs have been exploited recently for their antitumor properties <em>in vitro</em> and pose limited systemic adverse effects <em>in vivo.</em> Neutrophil-derived exosomes derived from immune cells can efficiently escape immune-surveillance and pass through the blood-brain barrier. They possess several intrinsic properties in drug delivery as they are nano-sized, extremely biocompatible, non-immunogenic, biodegradable, stable and can carry targeting agents with limited toxicity and display antitumor properties. Also, neutrophil-based nanotherapy is dependent on factors such as neutrophil kinetics and the physicochemical properties of NPs such as size, shape, and surface chemistry. Therefore, neutrophil-based drug delivery for cancer therapy via the use of polymer nanoparticles is widely studied as their clinical appliance in nanomedicine is still at its infancy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 18-32"},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895400","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":"Identification of pyroptosis-related gene S100A12 as a potential diagnostic biomarker for sepsis through bioinformatics analysis and machine learning","authors":"Shanshan Lin ,&nbsp;Jiayu Yan ,&nbsp;Shasha He ,&nbsp;Lianxiang Luo","doi":"10.1016/j.molimm.2025.04.009","DOIUrl":"10.1016/j.molimm.2025.04.009","url":null,"abstract":"<div><div>Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis and other forms of cellular demise. However, the role of pyroptosis in sepsis remains to be further explored. In this study, by employing a combination of the difference analysis, WGCNA, Friends' analysis, and machine learning, the central gene S100A12 was successfully identified. S100A12 demonstrated superb diagnostic capabilities in both the integrated and external validation datasets. Furthermore, significant disparities were observed in the levels of monocytes, eosinophils, and neutrophils between sepsis patients and the control group, as per the findings of immune infiltration analysis. The aforementioned immune infiltrating cells exhibited an increase in expression levels among patients diagnosed with sepsis and were found to be significantly and positively associated with S100A12 expression. The results of the single-cell analysis indicated a significant expression of S100A12 in both neutrophils and monocytes, which was in complete alignment with the outcomes of immune infiltration. In summary, the pyroptosis-related gene S100A12 represents a potential biomarker for the diagnosis and treatment of sepsis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 44-55"},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899463","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":"Tph cells are expanded in IgA vasculitis nephritis","authors":"Qinglian Jiang,&nbsp;Ziqi Su,&nbsp;Kaijun Zheng","doi":"10.1016/j.molimm.2025.04.012","DOIUrl":"10.1016/j.molimm.2025.04.012","url":null,"abstract":"<div><div>Ectopic lymphoid structures (ELSs) contribute to maintaining the chronic inflammation process of IgA vasculitis nephritis (IgAVN) and are associated with a more severe disease course. PD-1^hiCXCR5⁻CD4⁺ T peripheral helper (Tph) cells are recognized as the main CD4⁺ T cells that contribute to B cell immune responses and antibody production in ELSs. However, the role of Tph cells in the pathogenesis of IgAVN is currently unknown. Here, we showed that the frequency of circulating Tph (cTph) cells was higher in IgAV patients compared to healthy controls, and higher among those with nephritis than those without nephritis. In addition, the frequency of cTph cells was positively correlated with 24-hour urine protein and urine red blood cell levels in IgAVN patients. cTph cells from IgAVN patients expressed high levels of activation makers and B cell helper markers, including ICOS, Tigit, IL-21, and CXCL13, and induced memory B cell differentiation in vitro in the presence of IL-21. Taken together, these results suggest that PD-1^hiCXCR5⁻CD4⁺ cTph cells are involved in the pathogenesis of IgAVN by inducing B cell differentiation through IL-21, serving as a promising target for the treatment of IgAVN.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 12-17"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891107","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":"Dexmedetomidine improve lung inflammation by regulating autophagy and apoptosis of CD4+ T cell via AMPK/mTOR signaling","authors":"Renjie Luo ,&nbsp;Zhao Wang ,&nbsp;Fang Xu ,&nbsp;Ke Xie","doi":"10.1016/j.molimm.2025.04.011","DOIUrl":"10.1016/j.molimm.2025.04.011","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the protective effect and potential mechanism of dexmedetomidine (Dex) in acute lung injury (ALI).</div></div><div><h3>Materials and methods</h3><div>C57BL/6 mice and EL-4 cells were used for in vivo and in vitro studies, respectively. Cecal ligation and puncture (CLP) method was used to prepare an acute lung injury model. After dexmedetomidine intervention, tissue and cell samples were collected to evaluate and measure the severity of lung damage, the proportion of Treg cells, the expression of autophagy-related protein levels and AMPK/mTOR pathways.</div></div><div><h3>Results</h3><div>Dex reduced lung damage, and IL-17a, MPO positive cells in the lung, decreased the levels of pro-inflammatory cytokines, and restrain autophagy and apoptosis via the activation of the AMPK/mTOR pathway and increase of the proportion of Tregs.</div></div><div><h3>Conclusions</h3><div>Dex can inhibit the levels of autophagy and apoptosis, increase the proportion of Treg cells, and reduce CLP induced acute lung injury through regulating AKMP/MTOR pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891106","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":"Bro p 3, an nsLTP1: The first major allergen identified in Broussonetia papyrifera pollen","authors":"Zihan Jiang ,&nbsp;Xiaoling Yin ,&nbsp;Zhonglei Chen ,&nbsp;Shixi Liu ,&nbsp;Juan Meng ,&nbsp;Aiwu Xu","doi":"10.1016/j.molimm.2025.04.004","DOIUrl":"10.1016/j.molimm.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div><em>Broussonetia papyrifera</em> pollen is an important cause of allergy worldwide, yet its key allergenic components remain unclear. This study aims to identify and characterize the major allergen of <em>B.papyrifera</em> pollen.</div></div><div><h3>Methods</h3><div>Patients with allergic rhinitis (AR) symptoms in <em>B.papyrifera</em> pollen season and positive skin prick test (SPT) to <em>B.papyrifera</em> pollen extract were enrolled. Serum sIgE was measured by ImmunoCAP. The pollen crude extract was immunoblotted with patients’ sera. The major allergen was purified and subjected to mass spectrometry analysis. The cDNA of the allergen was cloned from a pollen cDNA library. The antigenicity of recombinant allergen was measured by ELISA. Overlapping peptides spanning the allergen were synthesized. Type 2 T cell epitopes were screened using patients’ PBMC by IL-4 ELISpot. Cross-reactivity of the allergen was evaluated.</div></div><div><h3>Results</h3><div><em>B. papyrifera</em>-sIgE was confirmed in 194 of 201 patients by ImmunoCAP. Bro p 3 was identified as major allergen by immunoblot. We purified, cloned the cDNA of, and determined the full-protein sequence of Bro p 3, an nsLTP1 with an average mass of 10264 Da. Recombinant Bro p 3 (rBro p 3) exhibited identical antigenicity as natural Bro p 3, with sensitization rates of 74.53 % and 78.89 %, respectively. Peptides Pep 7–21, Pep 10–24 and Pep 13–27 stimulated IL-4 secretion by T cells from 8, 9 and 8 out of 11 patients. Bro p 3-sIgE sensitization was significantly correlated to elevated sIgE of <em>B. papyrifera</em>, <em>Morus alba</em>, <em>Morus. rubra</em>, and <em>Humulus scandens</em>. It was also associated with the concurrence of conjunctivitis and conjunctivitis plus asthma. No IgE binding was found to the other two <em>B.papyrifera</em> nsLTPs. Bro p 3 inhibited the IgE binding to <em>M. alba</em> and <em>H. scandens</em> pollen extracts.</div></div><div><h3>Conclusions</h3><div>We demonstrated that Bro p 3 is the major allergen of <em>B. papyrifera</em> pollen and the first allergen from this species with its full sequence determined. The I₇-R₂₇ peptides of Bro p 3 represent its immunodominant type 2 T cell epitopes. Bro p 3 sensitization is relevant to clinical phenotypes and the cross-reactivity between <em>M. alba</em>, <em>H. scandens</em> and <em>B.papyrifera</em> pollen.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 160-170"},"PeriodicalIF":3.2,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877364","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":"Acid-sensing ion channel 1a promotes LPS-induced acute lung injury through the circRNA 18–658/miR-127–5p/TRIM72 axis","authors":"Yangyang Li ,&nbsp;Yueqin Zhu ,&nbsp;Zijun Liu ,&nbsp;Ruohan Ren ,&nbsp;Yuyan Wang ,&nbsp;Yuemei Li ,&nbsp;Anqi Zhang ,&nbsp;Hu Xu ,&nbsp;Ziwen Zhang ,&nbsp;Yuanyuan Tan ,&nbsp;Zhenxing Ding ,&nbsp;Yan Huang","doi":"10.1016/j.molimm.2025.04.002","DOIUrl":"10.1016/j.molimm.2025.04.002","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a serious disease with sudden onset, rapid progression, poor treatment response and high mortality. Acid-sensitive ion channels (ASICs) are a type of cation channel activated by extracellular acidification and are involved in the pathogenesis of inflammatory and immune diseases. Our previous research revealed that ASIC1a promotes ALI, but the specific mechanism is unclear. Circular RNAs (circRNAs) are a large class of noncoding RNAs that play important roles in the pathological processes of many diseases. However, their role in lipopolysaccharide (LPS)-induced ALI and their correlation with the ASIC1a channel remain unclear. In this study, via high-throughput sequencing, we investigated the effect of ASIC1a on circRNA expression. We focused on circRNA18–658 and its downstream signaling pathway in rat models of ALI. Our results revealed that ASIC1a promotes ALI through the circRNA18–658/miR-127–5p/TRIM72 axis, providing new targets and ideas for the study of the mechanism of ALI and the development of new drugs.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 150-159"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868675","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":"Ex vivo pre-activation shifts the in vivo differentiation of adoptively transferred CD8+ T cells in a melanoma model","authors":"Jinjin Lu ,&nbsp;Jianjun Hu ,&nbsp;Ziyao Zhao ,&nbsp;Xiuming Zhai ,&nbsp;Cheng Chen ,&nbsp;Xinyu Zheng ,&nbsp;Yanping Yang ,&nbsp;Yuhao Zheng ,&nbsp;Lilin Ye ,&nbsp;Qin Tian ,&nbsp;Yifei Wang","doi":"10.1016/j.molimm.2025.04.007","DOIUrl":"10.1016/j.molimm.2025.04.007","url":null,"abstract":"<div><div>Adoptive transfer of TCR-specific CD8⁺ T cells represents a powerful experimental platform for investigating tumor-specific CD8⁺ T cell responses within the framework of anti-tumor immunity. Genetic modulation of these transferred cells provides a robust strategy to elucidate the intrinsic molecular mechanisms underlying T cell differentiation and functionality, thereby offering critical insights to optimize tumor-specific CD8⁺ T cell antitumor immunity in cancer immunotherapy. A key aspect of this approach is the <em>ex vivo</em> activation of primary T cells, which raises important questions regarding the impact of pre-activation on subsequent T cell differentiation. In this study, we explored the differentiation trajectories of pre-activated CD8⁺ T cells and performed a comprehensive characterization of their epigenetic and transcriptional profiles using a murine melanoma model. Our findings revealed that <em>ex vivo</em> pre-activation not only attenuates progression towards terminal exhaustion in the tumor-draining lymph nodes (TdLNs) but also enhances the stem-like characteristics of CD8⁺ T cells within the tumor microenvironment (TME). Leveraging comprehensive ATAC-seq and RNA-seq analyses, we demonstrated that pre-activation modulates the epigenetic landscape and transcriptional profile of CD8⁺ T cells, fostering effector-related differentiation in the TdLNs while promoting stemness-associated programming in the TME. These findings highlight the profound influence of <em>ex vivo</em> pre-activation on the differentiation pathways of tumor-specific CD8⁺ T cells, underscoring the necessity of taking these experimental framework-induced discrepancies into consideration for more accurate data interpretation in relevant researches.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 139-149"},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860537","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":"Anti-inflammatory and antioxidative effects of Perilla frutescens-derived extracellular vesicles: Insights from Zebrafish models","authors":"Jinghong Huang ,&nbsp;Linxin Chen ,&nbsp;Wenhua Li ,&nbsp;Chih-Jung Chang","doi":"10.1016/j.molimm.2025.04.008","DOIUrl":"10.1016/j.molimm.2025.04.008","url":null,"abstract":"<div><div>Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we investigated the physicochemical characteristics, bioactive properties, and therapeutic potential of <em>Perilla frutescens</em>-derived exosome-like nanoparticles (PELNs). Transmission electron microscopy (TEM) revealed that PELNs exhibited a cup-shaped morphology, with a lipid bilayer and a size distribution ranging from 40 to 200 nm (mean: 68.4 ± 13.0 nm). The cargoes in PELNs were analyzed through multi-omics and small RNA sequencing. <em>In vivo</em> studies on zebrafish demonstrated that PELNs are non-toxic at experimental concentrations. A reduction in neutrophil migration to injured fins evidenced the anti-inflammatory properties of PELNs. Furthermore, a meta-analysis of transcriptomic data identified hundreds of differentially expressed genes (DEGs) across 12 samples of three experimental groups. These DEGs were annotated into three categories following gene ontology (GO) enrichment analysis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs were involved in immune-related pathways, including complement and coagulation cascades, systemic lupus erythematosus, PPAR signaling pathways, and antigen processing and presentation. Twelve selected DEGs were validated by quantitative real-time PCR (qRT-PCR), with particular confirmation of the <em>mpx</em> and <em>lcp1</em> genes via <em>in situ</em> hybridization. Furthermore, PELNs demonstrated antioxidative effects by mitigating reactive oxygen species (ROS) levels, as evidenced by measurements of four oxidative stress (OS) indicators (i.e., SOD, CAT, GSH, and MDA) in zebrafish larvae subjected to H₂O₂-induced OS. In summary, PELNs exhibit substantial anti-inflammatory and antioxidant properties, underscoring their potential as therapeutic agents for treating various inflammatory diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 126-138"},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855070","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":"Neferine reduces synovial inflammation and cardiac complications in a collagen-induced arthritis mouse model via inhibiting NF-κB/NLRP3 inflammasome axis","authors":"Jingjing Cao ,&nbsp;Huaxing Zhang ,&nbsp;Yanhui Ni ,&nbsp;Xiaoran Ning","doi":"10.1016/j.molimm.2025.04.001","DOIUrl":"10.1016/j.molimm.2025.04.001","url":null,"abstract":"<div><div>For the treatment of rheumatoid arthritis (RA), there are limited options for drugs with fewer side effects. Neferine possesses anti-inflammatory, anti-fibrotic, and cardioprotective properties, but its effectiveness in the treatment of RA remains unclear. Our study aimed to explore the impact of neferine administration on ankle joint inflammation and cardiac complications of collagen-induced arthritis (CIA) mice. The CIA model was introduced in male DBA/1 mice via subcutaneous injection of Type II collagen (CII) into the tail. We found that neferine alleviated ankle joint inflammation, cartilage erosion, and bone destruction, as well as reduced the levels of IL-6, TNF-α, IL-1β, and IL-18 in the serum of CIA mice. Furthermore, neferine reduced the expression of synovial damage markers (RANKL, MMP-3, and MMP-13) in the ankle joints of CIA mice. Mechanistically, neferine lowered the levels of NF-κB pathway-related molecules such as p-IκBα, p-p65, and nuclear p65 in the synovial tissue of CIA mice. Simultaneously, neferine reversed the upregulation of NLRP3, ASC, and cleaved-caspase-1 levels in the synovial tissue of CIA mice. Additionally, our results showed that neferine reduced the contents of myocardial injury markers (cTnI, CK-MB, and LDH), alleviated myocardial fibrosis, decreased expression of α-SMA and Collagen I, as well as mitigated the activation of fibrosis-related TGF-β/Smad signaling. In summary, our study demonstrates that neferine attenuates chondral and synovial inflammation in a CIA mouse model by inhibiting the activation of the NF-κB/NLRP3 inflammasome, and neferine has a protective effect on the hearts of CIA mice.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 117-125"},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855069","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}