Inflammation最新文献

{"title":"IL-18 Promotes the Development of Lupus Nephritis by Activating the Wnt/β-Catenin Signaling Pathway in Renal Tubular Epithelial Cells.","authors":"Jiashun Zeng, Yan Ting, Hong Yin, Si Yang, Lifen Xu","doi":"10.1007/s10753-026-02569-5","DOIUrl":"10.1007/s10753-026-02569-5","url":null,"abstract":"<p><p>This study investigates the specific role of interleukin-18 (IL-18) in lupus nephritis (LN) progression and its molecular mechanisms to provide a theoretical basis for the pathological intervention of LN. IL-18 levels were measured from systemic lupus erythematosus (SLE) patients with or without LN. MRL/lpr mice received intraperitoneal injection of IL-18 or its inhibitor to assess renal injury, inflammation, and Wnt/β-catenin pathway activity. In-vivo intervention experiments using Caspase-1 inhibitor (Ac-YVAD-CMK), Wnt pathway agonists (BML-284), and inhibitors (IWR-1-endo) were performed. In-vitro studies were conducted in human renal tubular epithelial cell line HK-2 to investigate the molecular mechanisms. IL-18 was markedly elevated in SLE patients, and further increased in urine and renal tissue of LN. In MRL/lpr mice, exogenous IL-18 significantly exacerbated renal injury, evidenced by increased urinary protein, serum creatinine, anti-dsDNA antibodies, tubulointerstitial inflammation, and increased activity index. This was accompanied by up-regulation of IFN-γ, IL-1β, IL-6, down-regulation of IL-10, and activation of the Wnt/β-catenin pathway (increased β-catenin, p-GSK-3β, and CK1α). Conversely, IL-18 blockade or Wnt inhibition attenuated these pathological changes. Notably, the protective effects of IL-18 inhibition were reversed by simultaneous Wnt activation. In-vitro, IL-18 promoted HK-2 cell proliferation and inflammatory secretion by activating Wnt/β-catenin signaling, effects which were blocked by a Caspase-1 inhibitor or a Wnt pathway inhibitor. IL-18 activated the Wnt/β-catenin signaling pathway in renal tubular epithelial cells and disrupted the balance of pro- and anti-inflammatory cytokine networks, thereby exacerbating tubulointerstitial inflammation and promoting renal injury in LN mice. These findings highlight the therapeutic potential of targeting the IL-18 signaling pathway in LN. Trial registration: Not applicable.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446003","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":"Crohn's Disease: From Immune Dysregulation to Intestinal Damage.","authors":"Silvia Salvatori, Rachele Frascatani, Pasquale De Vico, Irene Marafini, Giovanni Monteleone","doi":"10.1007/s10753-026-02561-z","DOIUrl":"10.1007/s10753-026-02561-z","url":null,"abstract":"<p><p>Crohn's disease (CD) is a long-lasting, recurring inflammatory bowel disease (IBD) marked by segmental, transmural inflammation that may affect any part of the gastrointestinal tract. Growing evidence suggests that CD does not originate from a single pathogenic mechanism, but instead results from the convergence of various biological disturbances that collectively disrupt intestinal homeostasis. Genetic alterations that weaken microbial detection, autophagy, and epithelial protection appear to establish initial vulnerabilities, enabling microbes to trigger exaggerated immune responses. This vulnerability is further exacerbated by environmental factors that intensify host microbial imbalance. The ensuing microenvironment fosters a significant production of effector molecules, which exacerbate the existing inflammation and activate stromal cells, which in turn drive tissue remodeling and structural complications such as ulceration, strictures, and fistulas. In this article, we synthesize the knowledge on the molecular and cellular mechanisms involved in CD pathogenesis, emphasizing the dynamic interplay between immune and stromal components that contributes to a disease-permissive environment. We also examine key inflammatory pathways and signaling networks involved in disease progression and discuss how these mechanistic insights inform existing and emerging therapeutic strategies.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420980","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":"Therapeutic Delivery of Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-143-3p Inhibits Myocardial and Systemic Inflammation and Attenuates Sepsis-Related Myocardial Injury.","authors":"Yuyang Qiu, Lian Liao, Tian Zhang, Yiming Ma, Jianyu Fu, Jiakai Wang, Xu Liu, Wei Xie","doi":"10.1007/s10753-026-02555-x","DOIUrl":"10.1007/s10753-026-02555-x","url":null,"abstract":"<p><p>Sepsis-related myocardial injury (SRMI) is a major contributor to mortality in septic patients, driven by uncontrolled inflammation and macrophage dysregulation. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) possess immunomodulatory properties, but their cardioprotective mechanisms remain unclear. Here, we investigated whether BMSC-Exos deliver microRNA-143-3p (miR-143-3p) to reprogram macrophages and attenuate SRMI. Exosomes were isolated from murine bone marrow mesenchymal stem cells and characterized by electron microscopy, nanoparticle tracking analysis, and immunoblotting. In lipopolysaccharide-stimulated macrophages, BMSC-Exos promoted a shift from pro-inflammatory M1 to reparative M2 polarization, and reduced pro-inflammatory cytokine secretion. In a mouse model of endotoxemia, BMSC-Exo administration improved seven-day survival, preserved cardiac function, decreased circulating myocardial injury markers, and increased the proportion of cardiac M2 macrophages. MicroRNA sequencing identified miR-143-3p as highly enriched in BMSC-Exos but downregulated in circulating exosomes from septic mice. Delivery of miR-143-3p mimics recapitulated the protective effects of BMSC-Exos, while inhibition of miR-143-3p exacerbated injury. Mechanistically, miR-143-3p directly targeted Toll-like receptor 4 (TLR4) and suppressed the downstream myeloid differentiation primary response 88/nuclear factor-κB (MyD88/NF-κB) signaling pathway. Furthermore, TLR4 knockdown phenocopied the anti-inflammatory and M2-polarizing effects of miR-143-3p. These findings indicate that BMSC-Exos attenuate SRMI by transferring miR-143-3p to macrophages, where it inhibits TLR4/MyD88/NF-κB signaling and promotes M2 polarization, highlighting a potential therapeutic strategy for septic cardiac injury.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420969","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: Aberrant Accumulation of Cell-Free DNA Activates the cGAS-STING-TBK1 Pathway of γδ T Cells to Promote the Inflammatory Responses in Oral Lichen Planus.","authors":"Xin-Yi Wei, Ya-Qin Tan, Gang Zhou","doi":"10.1007/s10753-026-02562-y","DOIUrl":"10.1007/s10753-026-02562-y","url":null,"abstract":"","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":"49 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404609","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":"Baricitinib Inhibits the Aggressive Phenotype of Synovial Fibroblasts in Rheumatoid Arthritis via the JAK-STAT3-EGR1 Axis.","authors":"Jing Wang, Yi Huang, Lingfei Mo, Fei Li, Xiaohao Wang, Yao Li, Ke Xu, Xinyi Liu, Hanchao Li, YuanYuan Li","doi":"10.1007/s10753-026-02557-9","DOIUrl":"10.1007/s10753-026-02557-9","url":null,"abstract":"<p><p>Synovial fibroblasts (SFs) transform into an aggressive phenotype in rheumatoid arthritis (RA), playing a significant role in sustaining synovitis and bone erosion. Baricitinib, a JAK inhibitor, has been validated as an effective treatment for RA. However, its direct inhibitory effects on RASFs remain poorly understood. The inflammatory response and aggressive behaviors (proliferation, apoptosis, migration, and invasion) of RASFs were assessed following treatment with varying concentrations of baricitinib. RNA sequencing was performed to identify differentially expressed genes and elucidate the impact of baricitinib on RASFs. The relationship between the JAK-STAT3 signaling pathway and downstream molecules (EGR1, BCL-2, MMP-2, MMP-9) was analyzed via western blotting. Collagen-induced arthritis (CIA) mice were treated with baricitinib via oral gavage or by intra-articular injection of shEGR1 to evaluate therapeutic efficacy. Baricitinib inhibited the production of inflammatory mediators in primary RASFs and reduced the progression of synovial inflammation and hyperplasia in RA patients as assessed by ultrasound. In vitro, baricitinib promoted apoptosis and inhibited the proliferation, migration, and invasion of RASFs, effects associated with decreased expression of the transcriptional regulator EGR1. In vivo, baricitinib effectively reduced arthritis scores, paw swelling, and the expression of inflammatory cytokines in the joint tissues of CIA mice. Similar therapeutic effects were observed upon inhibition of EGR1. Baricitinib inhibits the aggressive phenotype of RASFs through the JAK-STAT3-EGR1 axis, thereby contributing to the alleviation of the inflammatory response and joint destruction in RA.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404592","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":"Dehydrocostus Lactone Activates Nrf2 Signaling Pathway to Attenuate Oxidative Stress, Inflammation, and Excessive Autophagy in a Mouse Model of Chronic Obstructive Pulmonary Disease.","authors":"Dandan Liu, Yuehong Ma, Huihua Huang, Xuesong Cheng, Qian Ma, Jin Wang, Jin Zhang, Xueru Ge, Can Wu, Yue Wang, Xiaosong Chen, Yanbei Zhang","doi":"10.1007/s10753-026-02531-5","DOIUrl":"https://doi.org/10.1007/s10753-026-02531-5","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating respiratory disorder associated with high global mortality. Dehydrocostus lactone (DHLC), a natural sesquiterpene lactone derived from Saussurea lappa Clarke (a medicinal plant), possesses documented antioxidant and anti-inflammatory properties. This study aimed to investigate the potential therapeutic role and mechanism of action of DHLC in COPD. For in vivo experiments, male wild-type and Nrf2-knockout C57BL/6J mice were randomized into control, cigarette smoke extract (CSE), and CSE + DHLC treatment groups. Pulmonary function was assessed by measuring airway resistance and dynamic compliance Histopathological changes were assessed by hematoxylin and eosin staining, and emphysema severity was quantified by mean linear intercept and mean alveolar area measurements. Matrix metalloproteinase-9 (MMP-9) expression was detected by immunofluorescence, while oxidative stress markers superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were measured using commercial kits. For in vitro experiments, mouse alveolar epithelial MLE-12 cells were cultured and exposed to 5% CSE for 24 h. Cell viability was determined by CCK-8 assay, intracellular ROS generation was detected using the DCFH-DA probe, and inflammatory cytokine levels in cell supernatants and BALF were quantified by ELISA. Protein expression of Nrf2, HO-1, LC3, p62, and other targets was analyzed by western blotting; Nrf2 subcellular localization was visualized by immunofluorescence staining; and mRNA expression was measured by RT-qPCR. DHLC significantly improved pulmonary function, alleviated inflammatory cell infiltration and pulmonary emphysema, and reduced MMP-9 expression in the lungs of COPD mice. In both CSE-induced MLE-12 cells and murine COPD models, DHLC attenuated inflammation, oxidative stress, and excessive autophagy by decreasing pro-inflammatory factor levels, ROS generation, the LC3-II/I ratio, and MDA content, while increasing p62 expression and SOD activity. Furthermore, DHLC up-regulated Nrf2 and HO-1 expression and promoted Nrf2 nuclear translocation in CSE-exposed models. Most importantly, siRNA-mediated knockdown of Nrf2 abolished the protective effects of DHLC against CSE-induced inflammation, oxidative stress, and dysregulated autophagy. DHLC ameliorates CSE-induced COPD-like pathology in mice by attenuating oxidative stress, inflammation, and excessive autophagy through activation of the Nrf2 pathway.</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":"148396656","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":"Mitophagy in Metabolic Dysfunction-Associated Fatty Liver Disease: Mechanisms, Regulatory Networks, and Therapeutic Perspectives.","authors":"Zhiqiu Liu, Shuyang Zhang, Tianshu Zeng","doi":"10.1007/s10753-026-02548-w","DOIUrl":"10.1007/s10753-026-02548-w","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MASLD) represents the most prevalent chronic liver disorder globally, with pathogenesis closely linked to insulin resistance, obesity, and gut microbiota dysbiosis. Mitochondrial dysfunction is central to MASLD progression, and mitophagy-a selective form of autophagy that clears damaged mitochondria-plays a crucial role in maintaining cellular homeostasis. This review systematically delineates the molecular mechanisms, regulatory networks, and therapeutic implications of mitophagy in MASLD. We first outline the core machinery of mitophagy, encompassing both ubiquitin-dependent and ubiquitin-independent pathways. We then discuss how impaired mitophagy drives the disease progression of MASLD from the perspective of different hepatic cell types. Furthermore, we summarize the multilayered upstream regulatory network governing mitophagy in the context of MASLD, involving key signaling pathways, metabolic reprogramming, inflammatory cues, epigenetic modifications, and intercellular crosstalk. Finally, we examine therapeutic strategies targeting mitophagy-including clinical and preclinical agents, natural compounds, physical interventions, and emerging technologies-and highlight the challenges posed by its dualistic nature. Moving forward, integrating spatiotemporal dynamics with precision targeting will be essential to translate mitophagy modulation from mechanistic insight into viable clinical therapies for MASLD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396635","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":"Single-cell and Spatial Transcriptomic Profiling Reveal that LAPTM5-mediated Ferroptosis in Macrophages Induces Fibroblast Dysfunction and Amplifies Periodontal Inflammation.","authors":"Erli Wu, Xuan Yin, Yitong Chen, Jing Hu, Chongcheng Qiu, Chen Yang, Qian Chen, Peng Wang, Mengyuan Zhang, Misi Si, Rui Zhang, Qian Liu, Wei Shao, Lijie Fan, Qianming Chen, Peng Deng","doi":"10.1007/s10753-026-02559-7","DOIUrl":"10.1007/s10753-026-02559-7","url":null,"abstract":"<p><p>Periodontitis represents a persistent inflammatory condition marked by gradual damage to the gingival connective tissues and alveolar bone. Programmed cell death (PCD) is essential for preserving immune balance and includes various forms such as apoptosis, pyroptosis, necroptosis, and ferroptosis. Nevertheless, the principal PCD pathway that contributes periodontal inflammation has not been clearly identified. In this work, we integrated multiple publicly available single-cell RNA sequencing datasets and applied diverse gene set scoring approaches to systematically characterize the dynamic expression of PCD-associated genes in periodontitis-affected tissues. Ferroptosis emerged as one of the important PCD pathways, mainly occurring in macrophages. Cell-cell communication and spatial analyses suggested that ferroptotic macrophages were located adjacent to fibroblast-enriched regions and may interact with fibroblasts through Galectin and OSM signaling pathways. Functionally, ferroptotic macrophages suppressed fibroblast proliferation and migration while amplifying their pro-inflammatory response, underscoring their pivotal role in sustaining chronic inflammation. Furthermore, machine-learning analyses identified LAPTM5 as one of the ferroptosis-associated hub genes in macrophages. Knockdown of LAPTM5 in macrophages suppressed ferroptosis and subsequently attenuated fibroblast inflammatory responses. Collectively, our study highlights ferroptosis as one of the key pathogenic mechanisms in periodontitis and identifies LAPTM5-driven macrophage ferroptosis as a key driver of fibroblast dysfunction and chronic inflammation, providing potential therapeutic insights for restoring periodontal immune balance.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396622","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 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}