Inflammation最新文献

{"title":"A Self-Developed IL-6Rα Nanobody Alleviates Experimental Autoimmune Uveitis by Inhibiting Th1 and Th17 Cells.","authors":"Bochen Yao, Dali Tong, Jiaojiao Qian, Yuewei Peng, Zhouhuan Xi, Niannian Fan, Feiyu Jin, Can Deng, Bofeng Li, Kai Dong","doi":"10.1007/s10753-026-02540-4","DOIUrl":"https://doi.org/10.1007/s10753-026-02540-4","url":null,"abstract":"<p><p>Interleukin-6, a pleiotropic cytokine, initiates downstream signaling by binding to interleukin-6 receptor α (IL-6Rα) and glycoprotein 130 (GP130). Autoimmune uveitis, the most prevalent form of non-infectious uveitis, represents a serious sight-threatening ocular disorder. While corticosteroids remain the mainstay of treatment in clinical practice, their therapeutic utility is constrained by significant adverse effects. Emerging evidence highlights the pivotal role of IL-6 in autoimmune uveitis pathogenesis, particularly in promoting CD4⁺T cells differentiation into Type 17 helper T cells (Th17). In this study, we evaluated the therapeutic efficacy of a novel anti-IL-6Rα nanobody in experimental autoimmune uveitis (EAU) models. Peripheral blood mononuclear cells (PBMCs) from Vogt-Koyanagi-Harada (VKH) patients were used to further assess the translational relevance of the anti-IL-6Rα nanobody. Our results demonstrate that this nanobody not only suppressed Type 17 helper T cells but also Type 1 helper T cells (Th1). Furthermore, treatment with anti-IL-6Rα nanobody significantly reduced inflammatory mediators and ameliorated disease severity in murine models. In vitro studies using PBMCs from VKH patients revealed that the anti-IL-6Rα nanobody effectively suppressed both interferon-γ (IFN-γ) and IL-17 production. These findings collectively suggest that anti-IL-6Rα nanobody represents a promising therapeutic strategy for autoimmune uveitis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396526","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":"Pre-Treatment with Estradiol, But not Progesterone, Exacerbates DSS Colitis: Dysregulated Innate Immunity and Impaired Epithelial Damage Response.","authors":"Anja Hjelt, Lauri Polari, Heli Jokela, Pia Rantakari, Heidi Gerke, Diana M Toivola, Claes Ohlsson, Matti Poutanen, Jorma Määttä","doi":"10.1007/s10753-026-02554-y","DOIUrl":"10.1007/s10753-026-02554-y","url":null,"abstract":"<p><p>Epidemiological data have indicated an increased risk of inflammatory bowel disease associated with the female sex and contraceptive hormones. However, in preclinical models of estradiol in colitis, results have been inconsistent, and both alleviating and aggravating effects have been reported. Previously, we suggested that the estrogen receptor α mediates inflammation in the colon. Here, we investigated the effects of estradiol and progesterone in dextran sulphate sodium-induced colitis, using sham-operated or ovariectomized female mice with or without hormonal supplementation initiated three weeks before inflammation. We found that sham-operated, or ovariectomized mice supplemented either with only estradiol or estradiol and progesterone exhibited more severe intestinal inflammation compared to ovariectomized mice at day 7 of colitis. Simultaneously, progesterone supplementation of ovariectomized mice did not affect the inflammatory status. Estrogen receptors were expressed in several different cell types of the colonic mucosa, although at low levels. The estrogen receptor α was observed in the epithelium as well as in mononuclear phagocytes and T and B cells. The estrogen receptor β was found in the epithelium, and the G protein-coupled estrogen receptor in the lamina propria and vessel structures. Further, hormone depletion increased homeostatic immune cells, while estradiol exposure altered the expression of 791 genes involved in pathways promoting the antimicrobial response, immune cell activation, and metabolism related to epithelial integrity. With our results, we are the first to present strong and detailed evidence of estradiol as an inflammatory agent in the colon of female mice when allowing the appearance of longer-term effects.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375569","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":"ORMDL3 as Key Regulator of Endothelial Dysfunction in Atherosclerosis via Sphingolipid Biosynthesis.","authors":"Liyuan Wang, Yan Yun, Yu Song, Diming Zhao, Jinzhang Li, Shouji Zhang, Zhengjun Wang, Xiaochun Ma","doi":"10.1007/s10753-026-02546-y","DOIUrl":"10.1007/s10753-026-02546-y","url":null,"abstract":"<p><p>The ORMDL3 (ORMDL sphingolipid biosynthesis regulator 3) gene has been genetically and functionally linked to inflammatory conditions and atherosclerosis (AS). The aim of this study is to elucidate the regulatory role of ORMDL3 in endothelial inflammation, lipid homeostasis, and apoptosis within the context of AS. A recombinant adeno-associated virus (rAAV) encoding the D377Y mutant of human proprotein convertase subtilisin/kexin type 9 (rAAV/D377Y-mPCSK9) was used to induce atherosclerosis in mice and to assess the role of ORMDL3 in atherogenesis and vascular inflammation. Mechanistic studies were conducted using human umbilical vein endothelial cells (HUVECs) to evaluate the effects of ORMDL3 on endothelial inflammation, lipid metabolism, and apoptotic signaling. ORMDL3 expression was found to be elevated in aortic atherosclerotic lesions and in HUVECs exposed to pro-atherogenic stimuli. Genetic deletion of Ormdl3 in mice reduced plaque formation and vascular inflammation. In vitro, Ormdl3 knockdown suppressed the expression of adhesion molecules and proinflammatory cytokines, whereas its overexpression enhanced these responses, potentially through activation of the nuclear factor-kappa B (NF-κB) signaling pathway. ORMDL3 deficiency attenuated lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis through upregulation of ABCA1. Lipidomic profiling indicated increased ceramide and dihydroceramide levels in ORMDL3-deficient cells. Pharmacological inhibition of ceramide biosynthesis partially reversed ABCA1 upregulation, suggesting a lipid-mediated regulatory mechanism. Additionally, miR-34a-5p binds directly to ORMDL3 mRNA, downregulates its expression, and suppresses endothelial inflammation and apoptosis. Inflammatory stimulation led to downregulation of miR-34a-5p, indicating a feedback loop in ORMDL3 regulation. ORMDL3 contributed to endothelial dysfunction and plaque instability by modulating ABCA1-mediated lipid efflux, ER stress, inflammation, and apoptotic pathways. The regulatory involvement of ceramide biosynthesis and the miR-34a-5p/ORMDL3 axis provides additional insight into the molecular mechanisms underlying ORMDL3-mediated atherogenesis. Therapeutic strategies targeting ORMDL3 may enhance endothelial function and promote plaque stabilization in patients with AS. Trial RegistrationNot applicable.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368180","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":"The Dual Role of Exosomes in Gout: From Inflammatory Amplifiers to Therapeutic Regulators.","authors":"Xuege Gao, Jiawei Zhang, Xiaojuan Kong, Yanli Xue, Weimin Fan","doi":"10.1007/s10753-026-02551-1","DOIUrl":"10.1007/s10753-026-02551-1","url":null,"abstract":"<p><p>Gout is a metabolic disorder where excessive MSU crystals are found in joints and adjacent tissues. When the crystals are deposited acutely, they typically trigger loud and uncontrollable local inflammation. As we know, the main goals of diagnosis and treatment of the disease are the reduction of serum uric acid levels and treatment of acute inflammation. Although these methods are useful, we are still facing many challenges: early risk detection, personalized treatment plan and management of comorbidities associated with gout. As nanoscale vesicles for intercellular communication, exosomes are also receiving much attention due to their possible roles in the regulation of inflammation, pathogenesis and progression. We review the functions of exosomes in gout. Various mechanisms are known that exosomes regulate gouty inflammation. When immune cells activate MSU crystals, they release exosomes carrying mature IL-1β, NLRP3 inflammatory components and pro-inflammatory miRNAs that induce local inflammation. Exosomes from mesenchymal cells or other cell types may have other functions, such as NLRP3 inhibition and M2-polarized macrophage transporting the inflammation and tissue repair. It was carried out on vesicles collected from blood, synovial fluid, urine of patients for clinical studies. These vesicles differ in size, protein and miRNA expression because of the different stages of gout and could be the disease indicator. Most studies are still preliminary, small sample size and non-standard detection and evaluation. To translate these results into practice, more extensive prospective clinical trials are needed. Native and engineered exosomes are promising anti-inflammatory agents, modulating the immune system and facilitating precise tissue repair. Exosomes likely link MSU crystal deposition, acute inflammation and systemic immune metabolic dysregulation. Identifying the specific cell locations involved in gout is important for developing diagnostic and therapeutic approach for gout at earlier stages.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360620","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":"Opposing Dynamics of CD4 + Regulatory and CD8 + Foxp3+ T Cells Characterize Immune Imbalance in Rheumatoid Arthritis.","authors":"Baochen Li, Juanjuan Liu, Jing Li, Ruihe Wu, Yuxin Fan, Chong Gao, Caihong Wang","doi":"10.1007/s10753-026-02543-1","DOIUrl":"10.1007/s10753-026-02543-1","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by persistent inflammation and joint damage from impaired immune tolerance. While CD4 + regulatory T cells (Tregs) are key to immune balance, their ability to restore tolerance in RA remains insufficient. Recently, CD8 + Foxp3+T have emerged as distinct regulators of immune tolerance, and investigating their role may provide new insights into the pathogenesis of RA. We enrolled 51 RA patients and 27 healthy controls. RA patients were grouped by disease activity: low-to-moderate (L-M RA) or high (H RA). We analyzed clinical data and lymphocyte subsets, including CD4 + Tregs and CD8 + Foxp3+T, to identify key immunological differences between RA and HC. Internal validation was performed using bootstrapping, and P-values were adjusted for false discovery rate (FDR) to ensure robustness. (1) CD4 + Tregs decreased in RA, especially in H RA, while CD8 + Foxp3+T increased, most in L-M RA. (2) CD4 + Tregs correlated negatively with IL-2, IL-4, and IL-10, whereas CD8 + Foxp3+T correlated negatively with ESR, DAS28, and RF-IgA/IgG. (3) The CD4 + Treg/CD8 + Foxp3+T ratio distinguished RA from controls. The combined model (including TNF-α and CD4 + Treg%) demonstrated strong discrimination with an AUC of 0.928 (optimism-corrected AUC: 0.912). CD8 + Foxp3+ T were increased in patients with RA and exhibited a trend opposite to that of CD4 + Treg. These two cell populations were associated with disease activity from distinct immunological perspectives. Furthermore, the CD4 + Treg/CD8 + Foxp3+T ratio and the combination of CD4 + Treg% with TNF-α showed potential value in distinguishing patients with RA from healthy controls. These findings provide additional insight into the immunological characteristics of RA and support further investigation into the biological significance of CD8 + Foxp3+ T cells.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360577","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":"Integrated Multi-omics Profiling of 2,4-dinitrochlorobenzene (DNCB)-induced Atopic Dermatitis in Mice Reveals a Coordinated Network of Barrier Dysfunction, Immune Activation, and Metabolic Reprogramming.","authors":"Wenxiang Liu, Xu Li, Zhihui Wan, Jieshi Xie, Shu Wang, Yanhong Zhai, Zheng Cao, Ping Wang, Cheng Wang","doi":"10.1007/s10753-026-02553-z","DOIUrl":"10.1007/s10753-026-02553-z","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is caused by a combination of epidermal barrier defect and immune imbalance. However, the molecular networks between these structural abnormalities and metabolic variations are unclear. This study aim of this research was to examine the concurrent molecular alterations in skin barrier damage and metabolic disorders in an AD-like mouse model by a multi-omics strategy. A 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was established and the skin tissues were examined through the combination of transcriptomic, quantitative proteomic, and metabolomic analyses. Cross-omics correlation and network analyses were performed to identify consistently abnormal molecular pathways and crucial regulatory molecules. DNCB treatment caused severe epidermal hyperplasia, and prominent infiltration of CD3⁺ T cells, F4/80⁺ macrophages, and mast cells. Transcriptomic and proteomic analysis indicated significant disruption in keratinocyte differentiation, extracellular matrix organization, and cornified envelope formation pathways. Combined analysis detected 171 molecules which were simultaneously altered at both mRNA and protein levels, and network analysis identified FLG2 and KRT6B as central barrier-related molecules. Pathway enrichment analysis consistently showed the participation of AMPK and PPAR signaling pathways. Metabolomic analysis also revealed coordinated changes in lipid and amino acid metabolism which were closely associated with cornified envelope-associated genes and collagen-modifying enzymes. These findings indicate a close relationship between barrier, immune and metabolic regulation in DNCB-induced dermatitis and provide a multi-omics resource for future mechanistic studies of atopic skin inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338584","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":"A Dynamic and Complex Early Inflammatory Response in Blood and Cerebrospinal Fluid of Severe Traumatic Brain Injury Patients: A Dual Platform Analysis.","authors":"Oskar W Persson, Karsten Ruscher, Erik Uvelius, Niklas Marklund","doi":"10.1007/s10753-026-02549-9","DOIUrl":"10.1007/s10753-026-02549-9","url":null,"abstract":"<p><p>Severe traumatic brain injury (TBI) is associated with high mortality and long-term disability. Inflammation is central to TBI pathophysiology, yet early dynamics of inflammatory mediators in blood and cerebrospinal fluid (CSF) remain incompletely understood, and commonly used assay platforms have rarely been directly compared. We aimed to characterize the inflammatory response in blood and CSF during the first week after severe TBI and to assess agreement between electrochemiluminescence (ECL) and proximity extension assay (PEA). In this prospective observational study, adults with severe TBI (n = 21) were recruited. Plasma and CSF samples were collected at two time points: days 1-3 and days 4-8. Orthopedic patients with minor extremity fractures (n = 11) served as controls. Inflammatory mediator levels were quantified using ECL (11 mediators) and PEA (45 mediators). Group differences, temporal changes, and inter-platform agreement were analyzed. In plasma, 13 mediators were increased and 3 decreased, while in CSF, 19 were increased and 3 decreased during the first week post-injury. Key mediators (IL-6, IL-8, IL-10) were consistently elevated in both compartments. When comparing analytic methods, ECL and PEA showed strong cross-platform correlations for IL-8 and IL-10 in both plasma and CSF, whereas IL-13 showed weak, non-significant correlation. However, limited interchangeability between platforms and platform-related differences across compartments and time points were also observed. Severe TBI is associated with marked, temporal and compartmentalized inflammatory response during first post-injury, particularly in CSF. Comparison of ECL and PEA showed limited interchangeability, underscoring the importance of platform awareness and interpretation in TBI biomarker studies. Clinical trial number: Not applicable.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":"49 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338510","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":"Correction to:NMI Promotes Pro-Inflammatory Macrophage Polarization and Exacerbates Ulcerative Colitis.","authors":"Haoxue Yang, Jingjing Wang, Na Xu, Xiaoran Guo, Zhuangfeng Weng, Jierong Song, Zhenxing Chen, Min Zhang, Yaqi Gao, Xiaojie Zhao, Yongjie Yao, Yan You, Ce Tang, Yingfang Liu, Ping Lan, Huanhuan Liang","doi":"10.1007/s10753-026-02550-2","DOIUrl":"10.1007/s10753-026-02550-2","url":null,"abstract":"","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":"49 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301297","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":"Effects of TNF-α in Human Precision-Cut Liver Slices and its Implications for Metabolic Dysfunction-Associated Steatohepatitis Progression.","authors":"Ke Luo, Mei Li, Alan R Gorter, Dorenda Oosterhuis, Vincent E de Meijer, Peter Olinga","doi":"10.1007/s10753-025-02384-4","DOIUrl":"10.1007/s10753-025-02384-4","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) represents a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD), largely due to metabolic dysregulation and sustained liver inflammation. TNF-α plays a pivotal role in MASH pathogenesis by inducing cell death, inflammation, and decreased insulin sensitivity. In this study we investigated the effects of TNF-α in human precision-cut liver slices (PCLS) under healthy or steatotic conditions, to provide insights into MASH pathogenesis. PCLS were prepared from human liver tissue and cultured in control (WEGG) and hyper-nutritive (GFIPO) mediums with or without TNF-α (50 ng/mL) for 96 h. Viability was assessed via ATP content, lipid accumulation by triglyceride (TG) assay, and transcriptomic changes through Next-Generation Sequencing. The protein levels of cytokines, chemokines, and fibrotic mediators released from PCLS were quantified using Luminex assay and ELISA. TNF-α significantly altered the transcriptional profiles in PCLS, inducing pro-inflammatory and pro-fibrotic signaling, and downregulating lipid metabolic processes in both WEGG and GFIPO media. TNF-α showed a trend in elevating intracellular TG in both conditions, albeit not statistically significant. On protein levels, TNF-α supplementation to WEGG medium induced the expression of IL8, CCL2, CCL19, PDGF-AB/BB, TGF-α, and MMP9. GFIPO medium alone induced inflammatory and fibrotic responses indicated by elevated levels of IL8, CCL2, and Pro-collagen 1A1. GFIPO medium with TNF-α supplementation further exacerbated the inflammatory and fibrotic responses, characterized by increased release of cytokines and growth factors. This human PCLS model effectively demonstrated the co-occurrence of key features of MASH, such as steatosis, inflammation, and fibrosis, highlighting the impact of metabolic stress and inflammatory cytokine TNF-α on these disease characteristics, and the potential of the PCLS model in exploring mechanism of MASH progression.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301229","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":"Long Non-coding RNA TLX1NB Regulates Inflammatory Response in Periodontitis by Interacting With Matrix Metalloproteinase 8.","authors":"Shouxiang Yang, Wanting Yuan, Ziqiong Yang, Jiaxuan He, Xiaoqian Wang, Lei Lu, Zhijia Xu, Xiaoyu Yao, Chunai Zhan, Long Mei, Wanyu Zhang, Wei Shao, Xiaoyu Sun","doi":"10.1007/s10753-026-02541-3","DOIUrl":"10.1007/s10753-026-02541-3","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) play critical roles in regulating inflammatory responses in periodontitis. This investigation focused on the involvement of the lncRNA T cell leukemia homeobox 1 neighbor (TLX1NB) in periodontitis and its regulatory role in modulating matrix metalloproteinase 8 (MMP8). Transcriptome sequencing and RT-qPCR validation revealed a significant upregulation of TLX1NB in gingival tissues from patients with periodontitis. This upregulation was recapitulated in an in vitro inflammatory model using TNF-α-stimulated human gingival fibroblasts (HGFs). Both FISH and cellular fractionation assays demonstrated that TLX1NB is predominantly enriched in the nucleus of HGFs. Functionally, TLX1NB knockdown attenuated the production of key pro-inflammatory cytokines, including IL-1β, IL-6, and IL-8, in TNF-α-stimulated HGFs, while concurrently enhancing cell proliferation. Mechanistically, RNA pull‑down and RIP assays confirmed a direct molecular interaction between TLX1NB and MMP8, suggesting that TLX1NB may regulate MMP8 function through direct binding. Functional analysis further demonstrated that TLX1NB and MMP8 act cooperatively to regulate inflammatory responses and apoptosis in HGFs. Ultimately, our results show that reducing TLX1NB expression alleviates periodontitis-associated inflammation and cellular dysfunction. This effect is associated with MMP8 and correlates with decreased NF-κB signaling. Collectively, these findings highlight TLX1NB as a promising therapeutic target for the treatment of periodontal disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283417","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}