Molecular immunology最新文献

{"title":"KRT14 is a promising prognostic biomarker of breast cancer related to immune infiltration","authors":"Siqi Liao ,&nbsp;Xin Zhang ,&nbsp;Lanhui Chen ,&nbsp;Jianning Zhang ,&nbsp;Weiyu Lu ,&nbsp;Mengou Rao ,&nbsp;Yifan Zhang ,&nbsp;Zijian Ye ,&nbsp;Deyana Ivanova ,&nbsp;Fangfang Li ,&nbsp;Xuemei Chen ,&nbsp;Yingxiong Wang ,&nbsp;Anchao Song ,&nbsp;Biao Xie ,&nbsp;Meijiao Wang","doi":"10.1016/j.molimm.2025.02.016","DOIUrl":"10.1016/j.molimm.2025.02.016","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is the leading cancer among women globally, which has the highest incidence and mortality rate in over a hundred countries. This study was intended to discover a new prognostic biomarker, facilitating personalized treatment approaches.</div></div><div><h3>Methods</h3><div>RNA sequencing data from The Cancer Genome Atlas database and Gene Expression Omnibus database were utilized to download to evaluate expression levels and prognostic significance of Keratin 14 (KRT14). Methylation of KRT14 was also assessed. The CIBERSORT and single-sample gene set enrichment analysis algorithms were applied to explore the connection between KRT14 and the tumor microenvironment. Primary drugs' sensitivity and potential small molecule therapeutic compounds were analyzed through the \"pRRophetic\" R package and the Connectivity Map. The prognostic value of KRT14 was additionally corroborated through a comparison of protein levels in peritumoral and cancerous tissues via immunohistochemistry. Moreover, an immune-related prognostic model based on KRT14 was designed to enhance the prediction accuracy for the prognosis of BC patients.</div></div><div><h3>Results</h3><div>The study found that KRT14 expression was generally downregulated in BC, correlating strongly with poor prognosis. Compared to normal tissues, the methylation level of KRT14 was higher in BC tissues. Lower expression of KRT14 was linked to decreased anti-tumoral immune cells infiltration and increased immunosuppressive cells infiltration. Sensitivity to various key therapeutic drugs was lower in groups with diminished KRT14 expression. In addition, several potential anti-BC small molecule compounds were identified. The model designed in this study significantly enhanced the predictive capability for BC patients compared to predictions based solely on KRT14 expression levels.</div></div><div><h3>Conclusion</h3><div>Overall, KRT14 was closely correlated with the prognosis in BC, making it a reliable biomarker.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 55-73"},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488625","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":"Neem leaf extract alleviates LPS/D-GalN induced acute hepatitis in mice through its anti-inflammatory effects and activation of autophagy","authors":"Meiyu Jin ,&nbsp;LV Mengfan ,&nbsp;Hao Yu ,&nbsp;Jiaqi Cheng ,&nbsp;Yibo Zhang ,&nbsp;Yaxin Zhai ,&nbsp;Haihua Feng","doi":"10.1016/j.molimm.2025.02.015","DOIUrl":"10.1016/j.molimm.2025.02.015","url":null,"abstract":"<div><div>Acute hepatitis, characterized by rapid onset and high mortality, can result from infections, toxins, and other factors. However, current treatment options have significant side effects, necessitating further research into alternative therapies. This study investigated the extraction method of neem extract and found that its ethanolic extract effectively reduced mortality and decreased ALT and AST levels in mice serum, improving liver pathology. HPLC analysis identified azadirachtin and nimbolide in the extract. It also downregulated NF-κB, NLRP3, and p62 levels, while upregulating Lc3B and Atg5 levels. Experiments in Atg5 knockout mice showed that the absence of Atg5 weakened the extract's efficacy in reducing liver damage and inflammation and affected the extent of NLRP3 protein downregulation. However, it did not affect the extract's ability to reduce NF-κB. Overall, the ethanolic extract of neem leaves primarily modulates the inflammatory response through the NF-κB signaling pathway. The extract's efficacy in reducing NLRP3 is associated with autophagy. These discoveries offer a new theoretical basis for the role of neem in treating acute hepatitis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 33-43"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480690","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":"Artemisinin analogues are effective in the treatment of psoriasis by targeting RORγt","authors":"Xuyan Tian ,&nbsp;Fanrong Peng ,&nbsp;xiaoxiao xiong ,&nbsp;Xiaoting Xu ,&nbsp;Yu Zan ,&nbsp;Xinran Wang ,&nbsp;Bolan Yu ,&nbsp;Zhonghua Liu ,&nbsp;Xixin He ,&nbsp;Zhaofeng Huang","doi":"10.1016/j.molimm.2025.02.006","DOIUrl":"10.1016/j.molimm.2025.02.006","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin autoimmune disease. Th17 cells, when pathologically activated, significantly contribute to the progression of psoriasis. The symptoms of this skin condition could be notably alleviated by targeting and suppressing the activity of these cells. Retinoic acid receptor-associated orphan nuclear hormone receptor γ-t (RORγt), a critical transcription factor in Th17 cells, emerges as a promising therapeutic target for autoimmune conditions which are mediated by the dysregulation of these cells. In this study, we designed and synthesised a series of artemisinin analogues based on the chemical structure of artemisinin, and screened 3 compounds, QHS-1, QHS-2, and QHS-3, with better inhibition efficiency of RORγt activity. We found that each of the three artemisinin analogues were demonstrated efficacy in curbing IMQ-induced skin inflammation and the abnormal proliferation of keratinocytes within the <em>BALB/c</em> mouse model of psoriasis. Our findings indicate that the three artemisinin analogues not only effectively mitigated skin inflammation and the abnormal proliferation of keratinocytes in the IMQ-induced psoriasis model of <em>BALB/c</em> mice but also curtailed the infiltration of immune cells and the production of pro-inflammatory cytokines in the dermis. Furthermore, these compounds modulated the cytokine expression profiles within Th17 cells. They exerted a suppressive effect on the activity of Th17 cells by targeting RORγt, thereby dampening the inflammatory response in the dorsal skin of the mice. This inhibition led to a reduction in the pathological proliferation of keratinocytes. In conclusion, our research underscores the promising therapeutic potential of artemisinin analogues in the treatment of psoriasis, offering a slate of candidate compounds which could pave the way for novel drug development in this field.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 11-22"},"PeriodicalIF":3.2,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464678","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":"Andrographolide represses HIF-1α and VEGFA expression, thus inhibiting hypoxia-induced proliferation, oxidative stress, and inflammatory cytokine secretion in human keratinocytes","authors":"Hui Ma ,&nbsp;Fu Liu ,&nbsp;Youhua Fang","doi":"10.1016/j.molimm.2025.02.013","DOIUrl":"10.1016/j.molimm.2025.02.013","url":null,"abstract":"<div><div>Epidermal hypoxia, hyperproliferation of keratinocytes, and inflammation in skin lesions are relevant to the pathogenesis of inflammatory skin diseases, including psoriasis. Andrographolide (Andro) is a natural labdane diterpene with diverse biofunctions. Andro has been reported to alleviate psoriasis in mice. However, the exact mechanisms need further study. Our results demonstrated that Andro inhibited hypoxia-induced proliferation of human keratinocytes. Andro also protected the keratinocytes from hypoxia-induced oxidative stress and inflammatory response. Furthermore, we found that Andro suppressed the expression of HIF-1α and VEGFA expression in hypoxia-exposed keratinocytes. Overexpression of either HIF-1α or VEGFA attenuated the inhibitory effects of Andro on hypoxia-induced proliferation, oxidative stress, and inflammatory cytokine secretion. In summary, our results demonstrated that Andro protected keratinocytes from hypoxia-induced proliferation, oxidative stress, and inflammatory cytokine secretion by suppressing HIF-1α and VEGFA expression. Our findings provide an unreported insight into the potential use of Andro as an effective agent for the treatment of inflammatory skin diseases such as psoriasis in the future.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 23-32"},"PeriodicalIF":3.2,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464679","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":"Single-cell transcriptomics reveals the immune mechanisms by which tonsillectomy improves clinical outcomes of recurrent Immuoglobulin A nephropathy after kidney transplant","authors":"Qianyu Ye ,&nbsp;Ronghai Deng ,&nbsp;Jian Li ,&nbsp;Jiali Wang ,&nbsp;Xinhua Chang ,&nbsp;Huanxi Zhang ,&nbsp;Xutao Chen ,&nbsp;Jun Li ,&nbsp;Gang Huang ,&nbsp;Jiguang Fei ,&nbsp;Chenglin Wu ,&nbsp;Qian Fu ,&nbsp;Longshan Liu ,&nbsp;Guodong Chen ,&nbsp;Jiang Qiu ,&nbsp;Lizhong Chen ,&nbsp;Wenfang Chen ,&nbsp;Shicong Yang ,&nbsp;Suxiong Deng ,&nbsp;Yifang Gao ,&nbsp;Changxi Wang","doi":"10.1016/j.molimm.2025.02.010","DOIUrl":"10.1016/j.molimm.2025.02.010","url":null,"abstract":"<div><div>Immunoglobulin A nephropathy recurrence (IgANR) is a major cause of graft function loss in renal transplant patients with IgA nephropathy. Tonsillectomy has been recognized as an effective treatment for IgANR, but the cellular and molecular effects underlying its efficacy remain poorly understood. We aimed to identify the cell types and gene expression profiles in tonsillar tissue and peripheral blood mononuclear cells (PBMCs) to investigate the effectiveness of tonsillectomy in IgANR treatment. Flow cytometry and single-cell mRNA sequencing were performed to comprehensively characterize the cell types of 29 patients with IgANR. Additionally, we analyzed a tonsillar tissue sample and three PBMC samples to gain further insights. Single-cell transcriptome analysis revealed significant changes in gene expression following tonsillectomy in patients with IgANR. Conventional cytometry and transcriptome analysis revealed that B cells played a crucial role in IgANR treatment using tonsillectomy. Notably, the downregulation of <em>IGHA1</em> expression, memory B cell inactivation, and alterations in related pathways led to a reduction in galactose-deficient IgA1 (Gd-IgA1), which plays a crucial role in IgA nephropathy. The phosphatidylinositol-3-kinase (PI3k)-Akt pathway was significantly downregulated in peripheral B cells, and peripheral B cells in patients with IgANR who underwent tonsillectomy demonstrated downregulated expression of T cell leukemia/lymphoma 1 A (TCL1A), an Akt coactivator. As a result, it is possible that TCL1A plays a major role in the mediation of this therapeutic effect. Tonsillectomy aids in the treatment of IgANR by guiding B cell phenotypes, inducing functional changes, and regulating the immune response, thereby reducing Gd-IgA1 levels and improving clinical outcomes.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454617","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":"Conformational variants of I-Ak MHC class II molecules carry distinct immunopeptidomes","authors":"Lisa A. Drake ,&nbsp;Ramon Bossardi Ramos ,&nbsp;Lisa K. Denzin ,&nbsp;Padma P. Nanaware ,&nbsp;Lawrence J. Stern ,&nbsp;James R. Drake","doi":"10.1016/j.molimm.2025.02.009","DOIUrl":"10.1016/j.molimm.2025.02.009","url":null,"abstract":"<div><div>Major histocompatibility (MHC) class II molecules can exist in two distinct conformational states based on alternative pairing of transmembrane domain GxxxG dimerization motifs (i.e., M1- and M2-paired MHC class II). M1- and M2-paired MHC class II molecules drive different levels of T cell activation and B cell signaling; consequently, differential peptide loading would impact the level of immune response elicited by various antigens/epitopes. In previous studies of a single model antigen, we show that while peptide from BCR-bound antigen is selectively loaded onto M1-paired I-A^k class II, peptide from fluid phase processing of the same antigen is loaded onto both M1- and M2-paired I-A^k. To expand this analysis, we determined the immunnopeptidomes of M1-paired vs. total I-A^k class II molecules isolated from murine B cells. By comparing the two immunopeptidomes as well as the source proteins (antigens), a picture emerges highlighting the unique access each class II conformer has to antigens from different subcellular compartments. Sequence analysis of the two immunopeptidomes suggests a high degree of similarity between the peptide binding grooves of the two class II conformers. Analysis of class II-associated invariant chain (Ii)-derived peptides reveals the robust presence of a nested set of non-CLIP peptides that associate primarily with M1-paired class II, likely outside of the canonical peptide binding groove. In total, these results further highlight the differential peptide loading of M1- vs. M2-paired MHC class II molecules and support the idea that differential peptide loading could impact overall immune responsiveness.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 128-140"},"PeriodicalIF":3.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429547","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":"Ovalbumin alters DAF-16 Class-II/I gene expressions via insulin/insulin-like growth factor-1 signaling to initiate the innate immune response of Caenorhabditis elegans","authors":"Dong Liu ,&nbsp;Haibing Pei ,&nbsp;Kexin Yao ,&nbsp;Jinyan Gao ,&nbsp;Hongbing Chen ,&nbsp;Ping Tong","doi":"10.1016/j.molimm.2025.02.007","DOIUrl":"10.1016/j.molimm.2025.02.007","url":null,"abstract":"<div><div>Innate immunity, as a significant defense system of the body, plays a key role in allergic reactions, but the mechanism of how food allergens trigger innate immune signaling is still unclear. Ovalbumin (OVA) is a model allergen in food allergy studies. Previous studies by our group have demonstrated that the innate immunity of <em>Caenorhabditis elegans</em> (<em>C. elegans</em>) elicited by OVA treatment was related to the insulin/insulin-like growth factor-1 signaling (IIS) pathway, but the details remain unknown. Therefore, in this study, the molecular mechanism of innate immune signaling transduction of <em>C. elegans</em> stimulated by OVA was determined using genetic mutations as well as RT-PCR, GFP fluorescence visualization monitoring, and slow-killing experiments. Results showed that the expression levels of DAF-16-class-I/II genes in the IIS pathway were significantly changed in <em>C. elegans</em> after OVA treatment, and the upstream gene <em>daf-2</em> played an important role, which up-regulated the levels of DAF-16-class-II genes <em>dod-22</em> and F55G11.8 by the <em>daf-2</em>-<em>pqm-1</em> pathway, and down-regulated the level of DAF-16-class-I gene <em>thn-2</em> by the <em>daf-2</em>-<em>daf-16</em> pathway. Moreover, the upstream genes <em>daf-2</em> and <em>nhr-14</em>, and the transcription factors DAF-16, PQM-1, and SKN-1 in the IIS pathway all participated in the up-regulations of DAF-16-class-II genes <em>dod-17</em>, <em>dod-24</em>, and F55G11.2. In conclusion, details of OVA activating innate immunity in <em>C. elegans</em> through the IIS pathway are reported here, and the results can be further extrapolated to mammals, which will contribute to a better understanding of the mechanism of the occurrence of food allergic reactions from the perspective of innate immunity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 116-127"},"PeriodicalIF":3.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402994","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":"WISP1 promotes the progression of rheumatoid arthritis through NLRP3 inflammasome activation","authors":"Tiantian Hao ,&nbsp;Jianhua Niu ,&nbsp;Zizheng Tang ,&nbsp;Kangqi Xie ,&nbsp;Hongxia Chen ,&nbsp;Hui Wang","doi":"10.1016/j.molimm.2025.02.004","DOIUrl":"10.1016/j.molimm.2025.02.004","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease without effective treatments. This study explored WNT1 inducible signaling pathway protein 1 (WISP1) as a potential target to prevent RA.</div></div><div><h3>Methods</h3><div>AAV-shRNA-WISP1 or AAV-NC was injected in each ankle of collagen-induced arthritis (CIA) rats. Si-WISP1 or NC vector was transfected to TNF-α-induced fibroblast-like synoviocytes (FLSs). The effects of WISP1 knockdown on levels of pro-inflammatory factors in rats or FLSs were examined by qRT-PCR, ELISA, and western blot. CCK-8, Wound-healing, and transwell assays were used to estimate the effects of WISP1 knockdown on TNF-α-induced cell vitality, migration, and invasion in FLSs. The NLRP3 inflammasome-related proteins were checked by immunohistochemistry, immunofluorescence assay, and western blot in rats or FLSs.</div></div><div><h3>Findings</h3><div>Administration of WISP1 knockdown improved joint damage and diminished synovial inflammation in CIA rats. WISP1 knockdown restrained TNF-α-induced cell vitality, migration, and invasion in FLSs. In CIA rats and TNFα-induced FLSs, WISP1 knockdown reduced the secretion of inflammatory factors and restrained NLRP3 inflammasome activation.</div></div><div><h3>Interpretation</h3><div>WISP1 knockdown effectively inhibited NLRP3 inflammasome activation and inflammatory factors levels.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 106-115"},"PeriodicalIF":3.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386374","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":"Peripheral and central elevation of IL-8 in patients with Huntington’s disease","authors":"Jenny N. Fung ,&nbsp;John D. Lee ,&nbsp;Robert Adam ,&nbsp;John D. O’Sullivan ,&nbsp;Trent M. Woodruff","doi":"10.1016/j.molimm.2025.02.003","DOIUrl":"10.1016/j.molimm.2025.02.003","url":null,"abstract":"<div><h3>Objectives</h3><div>Huntington’s Disease (HD) is a debilitating neurodegenerative condition characterized by motor, cognitive and psychiatric abnormalities. Immune hyperactivity and dysregulation are common in HD. In addition to the central nervous system, HD patients exhibit systemic innate immune activation and inflammation, which has been shown to contribute to the pathogenic effects of the Huntingtin gene mutation. Upregulation of inflammatory mediators including interferon gamma (IFN-γ) and interleukin (IL)-8 has been observed in animal Huntington’s disease models. However, studies on HD patients remain limited.</div></div><div><h3>Methods</h3><div>In this study, serum samples from 58 HD patients and 59 age- and gender-matched healthy control individuals were analysed using a bead-based assay, that enabled simultaneous measurement of 13 cytokines and chemokines. Additionally, publicly available transcriptomic data from brain tissues of HD patients and controls were examined.</div></div><div><h3>Results</h3><div>Our results confirm that IL-8 protein levels are significantly higher in HD patients compared to non-HD controls, with the highest levels observed in the moderate HD group. In the control group, we found significant positive correlations between IL-8 levels and both IL-17A and IL-10. However, these correlations were not observed in HD patients, where IL-8 levels were notably positively correlated with pro-inflammatory markers including IFNγ and IL-23. Interestingly, IL-17A levels demonstrated a negative correlation with disease parameters, including CAG trinucleotide repeat expansion and disease burden score. Furthermore, cytokines and chemokines such as IFNγ and monocyte chemoattractant protein 1 (MCP-1; CCL2) demonstrated positive correlations with the same disease parameters. In-depth analysis of publicly available bulk RNAseq, and single-nucleus RNA-sequencing (snRNAseq) data from two key HD-affected brain regions- the prefrontal cortex and striatum revealed that <em>IL-8</em> expression is significantly increased in cortex samples from individuals with HD compared to non-HD controls. Moreover<strong>,</strong> snRNAseq data in the striatum showed higher <em>IL-8</em> expression in HD patients than in non-HD controls, with a predominant expression in microglia.</div></div><div><h3>Conclusion</h3><div>Overall, our findings support an upregulation of IL-8 in patients with HD, evident in both central degenerating brain regions, and peripheral blood samples. We identified unique immunological signatures associated with the severity of HD and provide potential biomarkers that may reflect immune-pathological mechanisms in HD patients.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 84-93"},"PeriodicalIF":3.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376713","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":"Synergistic therapeutic effect of parecoxib and ilomastat combination in osteoarthritis via inhibition of IL-17/PI3K/AKT/NF-κB activity","authors":"Xiaofei Feng ,&nbsp;Yao Ma ,&nbsp;Yuhao Zhao ,&nbsp;Zhenrui Zhao ,&nbsp;Zhengdong Song ,&nbsp;Li Lin ,&nbsp;Wenji Wang","doi":"10.1016/j.molimm.2025.02.005","DOIUrl":"10.1016/j.molimm.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis is a degenerative disease, and current drug treatment is to give nonsteroidal anti-inflammatory drugs to relieve symptoms. The anti-inflammatory ability of parecoxib and ilomastat has been confirmed, but the synergistic effect of combined administration in osteoarthritis has not been clear.</div></div><div><h3>Methods</h3><div>Mouse primary chondrocytes stimulated with IL-1β were cultured. The expression levels of inflammatory cytokines and matrix metalloproteinases were investigated by western blotting, quantitative real-time polymerase chain reaction and ELISA. The effects of parecoxib and ilomastat on chondrocyte apoptosis were evaluated by flow cytometry. In addition, the rat model of osteoarthritis was established by meniscal instability, and the morphological changes of cartilage and the expression levels of related molecules were monitored using Safranin O-Fast green and immunohistochemical staining after intra-articular injection of parecoxib, ilomastat, and the combination of the two.</div></div><div><h3>Results</h3><div>In vitro experiments showed that the combined administration of parecoxib and ilomastat more effectively inhibited the expression of proinflammatory factors and matrix metalloproteinases compared with single drug administration. The combined drug treatment could more effectively inhibit IL-1β-induced chondrocyte apoptosis. The combined drug treatment alleviated the progression of osteoarthritis by inhibiting the IL-17/PI3K/AKT/NF-κB pathway. In addition, in vivo experiments showed that the combined administration could improve the further deterioration of the osteoarthritis rat model.</div></div><div><h3>Conclusions</h3><div>The combined administration of parecoxib and ilomastat to inhibit IL-17/PI3K/AKT/NF-κB transduction is beneficial to reduce the infiltration of inflammatory factors and matrix metalloproteinases in osteoarthritis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 94-105"},"PeriodicalIF":3.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376453","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}