Inflammation Research最新文献

{"title":"Interleukin-37 modulates microglial phenotype and inhibits inflammatory response via the MyD88/NF-κB pathway in lipopolysaccharide-induced neuroinflammation.","authors":"Jingwen Zhang, Muhammad Abid Hayat, Yu Si, Tao Guo, Yinying Ni, Qian Wang, Yancheng Hong, Yudie Cao, Sijia He, Zijuan Weng, Fengmei Li, Hao Zuo, Xin Sun, Bo Chen, Jiabo Hu","doi":"10.1007/s00011-025-02048-x","DOIUrl":"https://doi.org/10.1007/s00011-025-02048-x","url":null,"abstract":"<p><strong>Objective: </strong>Interleukin-37 (IL-37), an anti-inflammatory cytokine within the interleukin-1 (IL-1) family, exhibits immunomodulatory properties. Here we evaluate the effects of IL-37 on microglia in neuroinflammation and its potential mechanisms.</p><p><strong>Methods: </strong>C57BL/6 mice were injected intraperitoneally with 1 µg of recombinant human IL-37 protein (rhIL-37), and 24 h later with lipopolysaccharide (LPS) (5 mg/kg) to induce neuroinflammation. After 2-h pretreatment of BV2 cells with rhIL-37 (100 ng/mL), an in vitro model was established by treating with LPS (100 ng/mL). Mice were assessed for behavioral tests, and neuronal damage was evaluated by Nissl staining and hematoxylin and eosin staining. The expression of Iba1, CD86, CD206, and NF-κB were detected by immunofluorescence staining, and inflammatory mediators and pathway proteins were evaluated by ELISA, qRT-PCR, and Western blot.</p><p><strong>Results: </strong>IL-37 significantly ameliorated LPS-induced behavioral deficits and protected mice from inflammatory injury. In vitro experiments suggested that IL-37 modulates polarization of microglia from M1 to M2 phenotype, along with reducing pro-inflammatory cytokine production. Moreover, IL-37 attenuated the production of NF-κB and MyD88.</p><p><strong>Conclusions: </strong>IL-37 regulates microglia against neuroinflammatory responses by blocking the MyD88/NF-κB pathway and shows for the first time how IL-37 influences the phenotype of microglia, suggesting a potential therapeutic target for neuroinflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"87"},"PeriodicalIF":4.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173613","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":"Aldosterone induces renal lymphangiogenesis through macrophage-lymphatic endothelial cell transformation and Inhibition by esaxerenone.","authors":"Haixia Guo, Ziqian Liu, Ruyan Lv, Boya Zhang, Panpan Qiang, Xuan Wang, Yi Chang, Fan Yang, Tatsuo Shimosawa, Qingyou Xu, Yunzhao Xiong","doi":"10.1007/s00011-025-02044-1","DOIUrl":"https://doi.org/10.1007/s00011-025-02044-1","url":null,"abstract":"<p><strong>Objective and design: </strong>Inflammation plays a crucial role in the occurrence and development of renal fibrosis. Lymphatic vessels have emerged as new hotspots in the domain of inflammation. Recent studies have revealed that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms. However, the underlying mechanisms of macrophage transdifferentiation into lymphatic endothelial cells (LECs) are still poorly understood.</p><p><strong>Methods: </strong>In vivo, thirty male Wistar rats were randomly divided into a sham group, an aldosterone group and an aldosterone + esaxerenone group. In vitro, Raw 264.7 cells and bone marrow-derived macrophages (BMDMs) were used. H&E, Masson, western blotting, immunohistochemistry, immunofluorescence, flow cytometry, and BMDM tube formation assays were used to assess renal fibrosis and lymphangiogenesis in a rat model of aldosterone-induced renal injury.</p><p><strong>Results: </strong>In this study, we observed pathological renal fibrosis and lymphangiogenesis in 12-week-old rats after aldosterone infusion. In addition, the treatment of rats with esaxerenone, a mineralocorticoid receptor blocker (MRB), significantly reduced renal lymphangiogenesis and fibrosis. Interestingly, we found that aldosterone can activate MR to stimulate macrophages to secrete vascular endothelial growth factor C (VEGF-C) and promote lymphatic angiogenesis.</p><p><strong>Conclusions: </strong>Our data suggest that renal fibrosis occurs in aldosterone-treated rats and that inflammation-induced macrophage transdifferentiation into LECs occurs during this process and that MRB attenuates renal fibrosis and lymphangiogenesis due to inflammatory injury.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"85"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142374","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":"Melatonin inhibits salivary gland epithelial cell ferroptosis via the NRF2/HO-1/GPX4 signaling pathway in primary Sjögren's syndrome.","authors":"Xiuhong Weng, Simin Wang, Qing Wang, Mingbo Wei, Bo Cheng","doi":"10.1007/s00011-025-02047-y","DOIUrl":"https://doi.org/10.1007/s00011-025-02047-y","url":null,"abstract":"<p><strong>Background: </strong>Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by xerostomia and autoimmune sialadenitis. Interferon-γ (IFN-γ) induces ferroptosis in salivary gland epithelial cells (SGECs), leading to salivary gland (SG) hypofunction. We previously demonstrated the beneficial effects of melatonin (MLT) in alleviating SG dysfunction and inflammation in a pSS animal model. However, the precise underlying mechanism remains unclear.</p><p><strong>Methods: </strong>Female NOD/ltj and ICR mice were used as the pSS mouse model and control group, respectively. MLT was administered via intraperitoneal injection to NOD/ltj mice to detect its effect on ferroptosis in SGs. Primary human SGECs and A253 cells were treated with IFN-γand ferroptosis inducers, with or without MLT.</p><p><strong>Results: </strong>Exogenous MLT alleviated pathological SG alterations and promoted saliva production through inhibiting SGEC ferroptosis. MLT inhibited SGEC ferroptosis induced by IFN-γ and ferroptosis inducers via nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 (NRF2/HO-1/GPX4) pathway activation. Moreover, MLT suppressed the nuclear factor-kappa B (NF-κB) pathway, which is triggered by ferroptosis in SGECs. Nevertheless, ML385-mediated NRF2 inhibition abrogated the antiferroptotic protective effects of MLT on SGECs.</p><p><strong>Conclusions: </strong>MLT inhibits SGEC ferroptosis through NRF2/HO-1/GPX4 pathway activation and thus attenuates ferroptosis-triggered NF-κB activity. Melatonin represents a potential therapeutic approach for pSS owing to its capacity to regulate ferroptosis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"84"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142403","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":"Influence of homocysteine on regulating immunothrombosis: mechanisms and therapeutic potential in management of infections.","authors":"Aswathy S Nair, Lloyd Tauro, Harshit B Joshi, Arnab Makhal, Teddy Sobczak, Julien Goret, Antoine Dewitte, Srinivas Kaveri, Harinath Chakrapani, Maria Mamani Matsuda, Manjunath B Joshi","doi":"10.1007/s00011-025-02045-0","DOIUrl":"10.1007/s00011-025-02045-0","url":null,"abstract":"<p><p>Mechanisms controlling innate immune responses and coagulation are interdependent, evolutionarily entangled and make a complex network to form immuno-thrombosis axis which is an integral part of host-defence response. During infections, immunothrombosis generates intravascular scaffold enabling recognition, trap and destruction of pathogens facilitating tissue integrity. However, the accompanying dysregulation fosters into pathologies associated with thrombosis and regulates severity, morbidity and mortality in infections. Several extrinsic and intrinsic factors such as (epi)genetic mechanisms, age, metabolism and lifestyle regulate immunothrombosis during infections. Mounting evidence demonstrates that homocysteine, a metabolic intermediate of methionine synthesis pathway activate cells participating in immuno-thrombosis such as neutrophils, platelets, monocytes and endothelial cells. Interestingly, multiple infections are significantly associated with perturbed homocysteine metabolism. In the present review, we describe mechanistic insights into how homocysteine drives immuno-thrombotic crosstalk that generate a vicious cycle of inflammation and coagulation that fuels organ failure during infections with an emphasis on sepsis, COVID-19, and other infectious diseases caused by parasites, viral, and bacterial pathogens. Subsequently, we discuss therapeutic strategies targeting homocysteine metabolism that may improve clinical outcomes in infections.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"86"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142378","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":"Lung contusion drives lung injury by modifying miRNA cargo in alveolar small extracellular vesicles.","authors":"Keita Nakatsutsumi, Dong Jun Park, Wooil Choi, William Johnston, Katie Pool, Jenny Kezios, Raul Coimbra, Brian P Eliceiri, Todd W Costantini","doi":"10.1007/s00011-025-02051-2","DOIUrl":"10.1007/s00011-025-02051-2","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the micro-RNA (miRNA) cargo of alveolar small extracellular vesicles (sEVs) after lung contusion (LC), which can contribute to the development of trauma-related acute lung injury (ALI).</p><p><strong>Methods: </strong>A mouse model of LC was conducted with a controlled cortical impact device. Bronchoalveolar lavage fluid (BAL) was collected 24 h post-injury and sEVs were purified using size exclusion chromatography. sEVs characteristics and miRNA cargo were analyzed with vesicle flow cytometry and sequencing. Macrophages were treated with BAL sEVs in vitro to assess their pro-inflammatory effect.</p><p><strong>Results: </strong>LC increased lung permeability and caused ALI histologically. LC increased the number of sEVs in the BAL and altered their miRNA cargo. BAL sEVs collected after LC increased pro-inflammatory cytokine release from macrophages.</p><p><strong>Conclusion: </strong>LC increased the mobilization of sEVs to the alveolar space and modified their miRNA cargo that might contribute to the development of ALI by activating the immune response in macrophages.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"83"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142402","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":"Bilirubin metabolism and its application in disease prevention: mechanisms and research advances.","authors":"Yue Zhang, Haoni Luan, Peng Song","doi":"10.1007/s00011-025-02049-w","DOIUrl":"https://doi.org/10.1007/s00011-025-02049-w","url":null,"abstract":"<p><p>The role of bilirubin, a product of heme metabolism, has evolved from a traditionally perceived metabolic waste product to a critical molecule with diverse biological roles. This article comprehensively reviews the metabolic functions of bilirubin and advances in its application for disease prevention. Bilirubin is primarily derived from hemoglobin catabolism in senescent erythrocytes. It is subsequently metabolized and excreted by the liver through tightly regulated processes involving enzymes, nuclear receptors, hormones, and pharmaceuticals. Bilirubin exhibits diverse physiological functions, including antioxidant, anti-inflammatory, and immunomodulatory activities. Owing to its unique chemical structure, bilirubin scavenges free radicals, inhibits lipid peroxidation, and protects cells across multiple systems. By suppressing the NF-κB signaling pathway, it reduces inflammatory factor release and mitigates chronic inflammation. Additionally, it modulates immune cell activity to maintain homeostasis, offering therapeutic potential for autoimmune and infectious diseases. Bilirubin demonstrates significant potential in disease prevention. In cardiovascular diseases, it attenuates atherosclerosis and mitigates myocardial ischemia/reperfusion injury. For metabolic disorders, it improves insulin resistance, regulates blood glucose, and reduces hepatic steatosis, offering therapeutic benefits for diabetes and non-alcoholic fatty liver disease. In neurological conditions, its antioxidant and anti-inflammatory properties hold promise for preventing and managing neurodegenerative diseases and neonatal bilirubin encephalopathy. Although research on bilirubin has advanced significantly, its intracellular targets and molecular interaction networks remain incompletely understood, and numerous challenges hinder its clinical translation. Future efforts should leverage multi-omics technologies to elucidate its mechanisms, develop intelligent and personalized therapeutics, and conduct large-scale clinical trials to accelerate translational applications and improve patient outcomes.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"81"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142376","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":"Lipopolysaccharide induces retention of E-cadherin in the endoplasmic reticulum and promotes hybrid epithelial-to-mesenchymal transition of human embryonic stem cells-derived expandable lung epithelial cells.","authors":"Türkan Portakal, Vítězslav Havlíček, Jarmila Herůdková, Vendula Pelková, Tereza Gruntová, Rıza Can Çakmakci, Hana Kotasová, Aleš Hampl, Petr Vaňhara","doi":"10.1007/s00011-025-02041-4","DOIUrl":"10.1007/s00011-025-02041-4","url":null,"abstract":"<p><strong>Background: </strong>Lipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration.</p><p><strong>Methods: </strong>ELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy.</p><p><strong>Results: </strong>We demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular β-catenin level through retention of E-cadherin within the endoplasmic reticulum.</p><p><strong>Conclusions: </strong>Human embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"82"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142400","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":"Targeting carboxypeptidase A/B activity with the phosphinic inhibitor C28 reduces the asthmatic response in a mouse model of house dust mite-induced asthma.","authors":"Venkata Sita Rama Raju Allam, David Montpeyó, Fabrice Beau, Sowsan Taha, Ida Waern, Srinivas Akula, Francesc Xavier Avilés, Julia Lorenzo, Laurent Devel, Gunnar Pejler, Sara Wernersson","doi":"10.1007/s00011-025-02046-z","DOIUrl":"10.1007/s00011-025-02046-z","url":null,"abstract":"<p><strong>Objective: </strong>Metallo-carboxypeptidases are implicated in several pathological contexts but their role in asthma and their potential as therapeutic targets in asthmatic settings are only partly understood. This study sought to investigate whether inhibition of carboxypeptidase activity of A and B-type could mitigate asthma-like symptoms in a mouse model of allergic airway inflammation.</p><p><strong>Methods: </strong>BALB/c mice were sensitized and challenged with repeated intranasal instillations of 10 µg house dust mite extract. Prior to each instillation, groups of mice received intraperitoneally from 0.2 to 1 mg/kg of compound 28, a phosphinic inhibitor of A/B-type carboxypeptidases. Manifestations of asthma-like features were assessed, including airway hyperresponsiveness, airway inflammation, lung histopathology and inflammatory markers.</p><p><strong>Results: </strong>Treatment with compound 28 protected against airway hyperresponsiveness and profoundly reduced the house dust mite-induced inflammation both in airways and in lung tissue. Moreover, compound 28 could mitigate airway smooth muscle and goblet cell remodelling as well as inflammatory gene expression in the lungs.</p><p><strong>Conclusions: </strong>Compound 28 could suppress multiple features of asthma in a physiologically relevant mouse model, reinforcing the potential of targeting A/B type carboxypeptidases for therapeutic purposes in allergic asthma.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"80"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142405","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":"Crosstalk between N6-methyladenosine modification and ncRNAs in rheumatic diseases: therapeutic and diagnostic implications.","authors":"Jianting Wen, Jian Liu, Lei Wan, Yue Sun, Fanfan Wang","doi":"10.1007/s00011-025-02034-3","DOIUrl":"https://doi.org/10.1007/s00011-025-02034-3","url":null,"abstract":"<p><strong>Background: </strong>In eukaryotic cells, N6-methyladenosine (m6A) is the most prevalent RNA methylation modification and plays a fundamental role in regulating diverse biological processes through the modulation of non-coding RNA (ncRNA) expression and activity. The role of m6A modification in developing rheumatic diseases is crucial but remains inadequately studied.</p><p><strong>Methods: </strong>Characterized by pain and inflammation, rheumatic diseases like rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) are autoimmune disorders. Recent findings emphasize the importance of m6A modifications and non-coding RNAs in the biological processes underlying rheumatic diseases.</p><p><strong>Results: </strong>This review elucidates the fundamental concept of m6A modification and the associated research methodologies. Subsequently, it systematically consolidates modern knowledge on the influence of m6A regulators and m6A modification-related ncRNAs on rheumatic diseases, incorporating perspectives on traditional Chinese medicine interventions.</p><p><strong>Conclusions: </strong>Offering a comprehensive overview of m6A-related ncRNAs in the context of rheumatic diseases, this review proposes new therapeutic avenues by targeting m6A modification pathways.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"79"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119640","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":"Paricalcitol promotes the maturation of immune granulomas in an experimental model of superoxide dismutase A-induced inflammation.","authors":"Ablyakimov Et, Kriventsov Ma, Kubyshkin Av, Maxim A Kriventsov","doi":"10.1007/s00011-025-02050-3","DOIUrl":"https://doi.org/10.1007/s00011-025-02050-3","url":null,"abstract":"<p><strong>Background: </strong>- Granulomatous inflammation is a hallmark of several chronic inflammatory diseases, characterized by the formation of immune granulomas. The vitamin D receptor (VDR) and its ligands, such as paricalcitol, have demonstrated immunomodulatory effects on various immune cell subpopulations, including macrophages, dendritic cells, and T-cells. However, the precise role of VDR activation in granuloma formation and the associated immune regulatory pathways, including the PD-1/PD-L1 axis, remains poorly understood. This study aimed to evaluate the effects of paricalcitol, a selective VDR agonist, on granuloma formation and immune cell composition in an experimental model of superoxide dismutase A (SoDA)-induced inflammation, with a focus on antigen-presenting cells (including CD68 + and CD1a + cells), T- and B-cell populations, and PD-L1 expression.</p><p><strong>Materials and methods: </strong>- The study involved 90 male Wistar rats divided into control and experimental groups. Experimental animals received paricalcitol intraperitoneally at different time points relative to sensitization with SoDA and complete Freund's adjuvant. Granulomatous infiltrates were evaluated histologically, and the cellular composition was assessed via immunohistochemistry using markers such as CD68, CD3, CD1a, CD20, and PD-L1. Statistical analysis included quantitative morphometry and group comparisons.</p><p><strong>Results: </strong>- Paricalcitol administration significantly influenced granuloma development, with groups receiving treatment before (E1) or at the time of sensitization (E2) showing a reduction in immature granulomas and an increase in mature granulomas compared to the control groups. Enhanced macrophage differentiation, characterized by increased multinucleated giant cells and epithelioid cells, was observed. Additionally, there was a significant increase in PD-L1 expression in granulomatous infiltrates of treated groups, particularly in peripherally located immune cells. These effects were accompanied by a modulation of T-cell responses, including a reduction in CD3 + T-cell population.</p><p><strong>Conclusion: </strong>- The findings suggest that paricalcitol promotes granuloma stabilization and maturation by modulating VDR-mediated immune pathways, including maturation and transformation of macrophages into epithelioid and giant multinucleated cells, increase in number of CD1a + cells, and PD-1/PD-L1 axis regulation. The ability of paricalcitol to enhance PD-L1 expression through the VDR-mediated pathways provides additional evidence for its role in preventing excessive immune responses and highlights the therapeutic potential of VDR agonists in managing granulomatous inflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"78"},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989738","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}