Inflammation Research最新文献

{"title":"Extracorporeal photopheresis induces the release of anti-inflammatory fatty acids and oxylipins and suppresses pro-inflammatory sphingosine-1-phosphate.","authors":"Gerhard Hagn, Ara Cho, Nina Zila, Barbara Sterniczky, Christian Jantschitsch, Dexin Dong, Andrea Bileck, Mariia Koren, Philipp Paulitschke, Thomas Mohr, Robert Knobler, Wolfgang Peter Weninger, Christopher Gerner, Verena Paulitschke","doi":"10.1007/s00011-025-02007-6","DOIUrl":"10.1007/s00011-025-02007-6","url":null,"abstract":"<p><strong>Aims: </strong>Extracorporeal photopheresis (ECP) is a UVA-based phototherapy of whole blood and well established as a first line or combination therapy for the treatment of cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease and is used to control organ transplant rejection. While the proapoptotic activity on activated T-cells is evident, the clinical efficacy of this treatment also appears to be based on other yet unknown mechanisms. In this study, we aimed to identify novel mechanisms of ECP regardless of the patient's background situation.</p><p><strong>Main methods: </strong>To better understand the immediate consequences of ECP, we analyzed blood plasma of patients with different ECP indications immediately before and after treatment with regard to proteins and lipid mediators.</p><p><strong>Key findings: </strong>While proteome profiling identified substantial inter-individual differences in the protein composition, no significant alteration was detectable upon treatment. In contrast, several fatty acids and lipid mediators were found to be significantly altered by ECP. Remarkably, upregulated lipid mediators including polyunsaturated fatty acids, 12-HEPE and 13-OxoODE have been described to be anti-inflammatory, while the downregulated molecules sphingosine-1-phosphate (S1P) and stearic acid are potent pro-inflammatory mediators. A selective sphingosine-1-phosphate-1 receptor (S1P1) modulator AUY954, which decreases S1P1 and experimentally reduces transplant rejection in vivo, showed greater anti-proliferative activity in human lung fibroblasts from COPD patients compared to normal lung fibroblasts, confirming that this pathway may be important in ECP and its mode of action.</p><p><strong>Significance and outlook: </strong>In conclusion, we suggest that the ECP-induced changes in lipid mediators may contribute to the remarkable anti-inflammatory effects of the treatment. Depending on their lipid status, patients may benefit from novel treatment regimens combining ECP with lipid modulators. This could be used for the prevention of transplant organ rejection, the treatment of acute or chronic GvHD or transplant organ rejection and the long-term treatment of various skin diseases. This study uncovers novel mechanisms of ECP, that can be used to establish clinically relevant lipid profiles of patients to support patient stratification, predictive or prognostic purposes and thus personalized medical care in the framework of PPPM practice. A combination with S1P modulators may therefore have beneficial effects.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"40"},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407205","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":"The causal effect of natural killer cells on COVID-19 infection, hospitalization and severity.","authors":"Kaili Yang, Jun Quan, Zhi Liu, Zebing Huang, Shuyi Wang, Jia Li, Aiming Wang, Li Wu, Songman Yu, Panpan Yi, Meifang Xiao, Yayu Chen, Xingwang Hu, Shushan Zhao","doi":"10.1007/s00011-024-01967-5","DOIUrl":"10.1007/s00011-024-01967-5","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have suggested that alterations in natural killer (NK) cell function may contribute to the development of COVID-19. Additionally, dysregulated NK cells may increase susceptibility to COVID-19 and affect the severity of the infection.</p><p><strong>Purpose: </strong>This study aimed to explore the causal relationship between NK cell-related immune traits and the risk of COVID-19 infection.</p><p><strong>Methods: </strong>A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship between NK cell-related immune traits and COVID-19. Exposure and outcome data were analyzed using the two-sample Mendelian Randomization (MR) method.</p><p><strong>Results: </strong>The results of the study suggest that there is a causal relationship between the absolute number of NK cells in COVID-19 infection and the risk of severe illness. The results also demonstrated that the morphological parameters are not causally related to COVID-19 infection but were causally related to COVID-19 hospitalization and COVID-19 severity.</p><p><strong>Conclusion: </strong>This finding has important implications for our understanding of the pathophysiology of COVID-19 and the development of future therapies and interventions for this disease.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"37"},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407310","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":"Group 2 innate lymphoid cells derived IL-9 reduces macrophage apoptosis and attenuates acute lung injury in sepsis.","authors":"Xiaohui Zhong, Jingyi Jin, Hang Zhang, Zhicong Liu, Yichao Ren, Yi Xiao, Yuebai Zhang, Sisi Yang, Shu Fang, Nan Lin, Ping Cui, Daqing Ma, Qiang Shu, Dengming Lai","doi":"10.1007/s00011-024-01978-2","DOIUrl":"10.1007/s00011-024-01978-2","url":null,"abstract":"<p><strong>Background: </strong>Group 2 innate lymphoid cells (ILC2) are the main group of tissue-resident ILCs in the lungs, which protect airway barrier integrity following infection. Macrophages are integral to the regulation of immune homeostasis in sepsis. However, the relationship between ILC2 and macrophages in the context of sepsis induced acute lung injury remains uncertain.</p><p><strong>Methods: </strong>The sepsis was conducted by cecal ligation and puncture (CLP) model in Wild Type (WT) mice and ILC2 depleted mice. Septic mice were injected intratracheally IL-9, and the frequency and markers expression of ILC2 and macrophage were measured by Flow cytometry and CyTOF. The lung injury was conducted with pathological analysis. In vitro studies, MH-S cells were exposed to LPS with/without interleukin-9 (IL-9), and mTOR level and MH-S cells death were measured with western bloting or Flow cytometry.</p><p><strong>Results: </strong>Sepsis induced the accumulation of ILCs and pulmonary macrophages in lungs. Furtherly, we revealed that ILC2 and CD45⁺F4/80⁺CD11c⁺ macrophages expanded during sepsis induced acute lung injury. Meanwhile, ILC2 depletion significantly enhanced macrophages expansion. In vivo and in vitro studies determined that pulmonary macrophage death followed by sepsis were protedced by IL-9, which was main secreted by ILC2 in lung. Furthermore, IL-9 significantly declined the expression of mTOR, and the presence of ILC2 or IL-9 reduced the expression of M1 markers (CD86 or MHC II).</p><p><strong>Conclusions: </strong>IL-9 secreted by ILC2 has a protective role in sepsis induced lung injury by reducing macrophage apoptosis and M1 polarization via mTOR.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"38"},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407227","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":"IL-27 regulates macrophage ferroptosis by inhibiting the Nrf2/HO1 signaling pathway in sepsis-induced ARDS.","authors":"Meng Xiong, Renjie Luo, Zhijiao Zhang, Panting Liu, Qiaozhi Peng, Fang Xu, Minkang Guo","doi":"10.1007/s00011-024-01986-2","DOIUrl":"10.1007/s00011-024-01986-2","url":null,"abstract":"<p><strong>Objectives: </strong>Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced ARDS.</p><p><strong>Methods: </strong>A cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R^-/- mice. Then, the mice were randomly divided into 4 groups: a control group, a CLP group, an IL-27 + CLP combination group, and an IL-27, CLP, and Oltipraz combination group. RAW 264.7 cells and BMDMs were used to further determine the role and mechanism of IL-27 in vitro.</p><p><strong>Results: </strong>In vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R^-/- mice, the effects of IL-27 were abrogated. Oltipraz inhibited IL-27-induced changes by up-regulating Nrf2 expression. Overall, this present study demonstrated that the combination of IL-27 and LPS-induced macrophage ferroptosis, promoted macrophage M1 polarization, and inhibited M2 polarization by inhibiting the Nrf2/HO-1 pathway.</p><p><strong>Conclusion: </strong>Oltipraz may alleviate ARDS-related lung injury by up-regulating Nrf2 expression and concurrently inhibiting macrophage ferroptosis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"39"},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407308","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":"Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.","authors":"Daniel Svensson, Bengt-Olof Nilsson","doi":"10.1007/s00011-025-02005-8","DOIUrl":"10.1007/s00011-025-02005-8","url":null,"abstract":"<p><strong>Background: </strong>Human cathelicidin LL-37 shows activity towards both gram-positive and gram-negative bacteria, and it is also active against some types of viruses. Besides its antimicrobial effects, the peptide modulates innate immunity through binding and inactivation of bacterial endotoxins and promoting chemotaxis of immune cells.</p><p><strong>Results: </strong>LL-37 is reported to interact with plasma membrane receptors and mediate import of Ca²⁺. Importantly, LL-37 has both anti- and pro-inflammatory effects. LL-37 is cytotoxic to many different human cell types, particularly infected cells, when administered to the cells at final concentrations of 1-10 µM. In psoriatic lesions very high concentrations (300 µM) of the peptide are detected, and in periodontitis, gingival crevicular fluid contains about 1 µM LL-37, implying high concentrations of the peptide at the site of infection/inflammation which can affect host cell viability locally.</p><p><strong>Conclusions: </strong>Altogether, LL-37 may inhibit and prevent the infection from spreading by direct anti-bacterial and anti-viral effects, but also via anti- and pro-inflammatory mechanisms, and through killing already infected and weakened host cells at the site of infection/inflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"36"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597045","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":"SIRT6 inhibits endoplasmic reticulum stress-mediated ferroptosis by activating Nrf2/HO-1 signaling to alleviate osteoarthritis.","authors":"Jiaqi Shi, Li Chen, Xu Wang, Xin Ma","doi":"10.1007/s00011-025-01998-6","DOIUrl":"10.1007/s00011-025-01998-6","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is a prevalent joint disease featured by articular cartilage destruction, causing a huge socio-economic burden worldwide. Repressing endoplasmic reticulum stress (ERS)-mediated ferroptosis can alleviate the progression of OA. Sirtuin 6 (SIRT6) has been shown to suppress OA, but whether SIRT6 can regulate ferroptosis in OA through ERS remains unclear.</p><p><strong>Methods: </strong>In this study, both in vivo and in vitro models of OA were constructed. Micro-CT scans and three-dimensional reconstruction were used to observe the structural injury of knee joint in mice. H&E, TB, SOFG and TUNEL staining were employed to conduct pathological examination of cartilage tissues. The levels of inflammatory factors were analyzed using ELISA. Besides, ERS was assessed by detecting the levels of ERS-related proteins using immunohistochemistry, immunoblotting and immunofluorescence staining. Iron deposition in cartilage tissues was tested by prussian blue staining. Moreover, the contents of intracellular ROS, lipid ROS and Fe²⁺ were evaluated in IL-1β-stimulated C28/I2 cells. Finally, ML385 (an inhibitor of Nrf2) or tunicamycin (an agonist of ERS) was added to C28/I2 cells to elucidate the exact mechanism.</p><p><strong>Results: </strong>SIRT6 upregulation reduced the structural injury and inflammation in cartilage tissues of OA mice. ERS and ferroptosis were inhibited by SIRT6 overexpression in cartilage tissues of OA mice and C28/I2 cells exposed to IL-1β. Additionally, SIRT6 upregulation activated Nrf2/HO-1 signaling, as evidenced by elevated nuclear Nrf2 and HO-1 expression. Further, ML385 treatment attenuated the impacts of SIRT6 overexpression on inflammation, ERS and ferroptosis in C28/I2 cells under IL-1β conditions. Particularly, tunicamycin intervention blocked the effects of SIRT6 upregulation on ferroptosis in IL-1β-treated C28/I2 cells.</p><p><strong>Conclusions: </strong>Collectively, SIRT6 inhibits ERS-medicated ferroptosis through activation of Nrf2/HO-1 pathway in chondrocytes to alleviate OA.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"35"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382479","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":"HMGB1: key mediator in digestive system diseases.","authors":"Hengqian Liu, Xiping Liao, Zuo Zhang, Qian Min, Yuanyuan Li, Junzhi Xiong, Qiao Lv, Xia Xie, Jianyun Zhou, Zhongli Liao, Hongli Zhou","doi":"10.1007/s00011-025-02002-x","DOIUrl":"https://doi.org/10.1007/s00011-025-02002-x","url":null,"abstract":"<p><p>High Mobility Group Box 1 (HMGB1), a multifunctional non-histone protein, and its involvement in various physiological and pathological contexts has garnered significant attention. Given HMGB1's central function in modulating key biological activities, such as inflammatory responses and cellular death, its contribution to the pathogenesis of digestive system diseases has become a focus of growing interest. This review aims to comprehensively explore the mechanisms by which HMGB1 contributes to the progression of inflammatory bowel disease (IBD), liver disorders, and pancreatitis. Furthermore, we explore the prospective clinical applications and outline future research directions for HMGB1 in digestive diseases, providing fresh perspectives that highlight the necessity of ongoing studies to understand its role in these conditions.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"34"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189122","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":"Silicone breast implant-associated pathologies and T cell-mediated responses.","authors":"Puja Jagasia, Iulianna Taritsa, Kazimir Bagdady, Shivani Shah, Megan Fracol","doi":"10.1007/s00011-025-02006-7","DOIUrl":"https://doi.org/10.1007/s00011-025-02006-7","url":null,"abstract":"<p><p>Silicone breast implants elicit a foreign body response (FBR) defined by a complex cascade of various immune cells. Studies have shown that the capsule around silicone breast implants that forms as a result of the FBR contains large T cell populations. T cells are implicated in pathologies such as capsular contracture, which is defined by an excessively fibrotic capsule, and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a non-Hodgkin's lymphoma. In this article, we provide a synthesis of 17 studies reporting on T cell-mediated responses to silicone breast implants and highlight recent developments on this topic. The lymphocytes present in the breast implant capsule are predominantly Th1 and Th17 cells. Patients with advanced capsular contracture had fewer T-regulatory (Treg) cells present in the capsules that were less able to suppress T effector cells such as Th17 cells, which can promote fibrosis in autoimmune conditions. Textured silicone implants, which are associated with BIA-ALCL, created a more robust T cell response, especially CD30 + T cells in the peri-implant fluid and CD4 + T cells in the capsule. Cultivating a deeper understanding of T cell-mediated responses to silicone breast implants may allow for novel treatments of breast implant-associated complications and malignancies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"33"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074317","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":"A window into intracellular events in myositis through subcellular proteomics.","authors":"Jennifer M Peterson, Valérie Leclair, Olumide E Oyebode, Dema M Herzallah, Andrea L Nestor-Kalinoski, Jose Morais, René P Zahedi, Mazen Alamr, John A Di Battista, Marie Hudson","doi":"10.1007/s00011-025-01996-8","DOIUrl":"10.1007/s00011-025-01996-8","url":null,"abstract":"<p><strong>Objective and design: </strong>Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of inflammatory muscle disorders of unknown etiology. It is postulated that mitochondrial dysfunction and protein aggregation in skeletal muscle contribute to myofiber degeneration. However, molecular pathways that lead to protein aggregation in skeletal muscle are not well defined.</p><p><strong>Subjects: </strong>Here we have isolated membrane-bound organelles (e.g., nuclei, mitochondria, sarcoplasmic/endoplasmic reticulum, Golgi apparatus, and plasma membrane) from muscle biopsies of normal (n = 3) and muscle disease patients (n = 11). Of the myopathy group, 10 patients displayed mitochondrial abnormalities (IIM (n = 9); mitochondrial myopathy (n = 1)), and one IIM patient did not show mitochondrial abnormalities (polymyositis).</p><p><strong>Methods: </strong>Global proteomic analysis was performed using an Orbitrap Fusion mass spectrometer. Upon unsupervised clustering, normal and mitochondrial myopathy muscle samples clustered separately from IIM samples.</p><p><strong>Results: </strong>We have confirmed previously known protein alterations in IIM and identified several new ones. For example, we found differential expression of (i) nuclear proteins that control cell division, transcription, RNA regulation, and stability, (ii) ER and Golgi proteins involved in protein folding, degradation, and protein trafficking in the cytosol, and (iii) mitochondrial proteins involved in energy production/metabolism and alterations in cytoskeletal and contractile machinery of the muscle.</p><p><strong>Conclusions: </strong>Our data demonstrates that molecular alterations are not limited to protein aggregations in the cytosol (inclusions) and occur in nuclear, mitochondrial, and membrane compartments of IIM skeletal muscle.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"31"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074310","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":"Histamine and TH2 cytokines regulate the biosynthesis of cysteinyl-leukotrienes and expression of their receptors in human mast cells.","authors":"Patricia Gehlhaar, Katrin Schaper-Gerhardt, Ralf Gutzmer, Franziska Hasler, Till A Röhn, Thomas Werfel, Susanne Mommert","doi":"10.1007/s00011-024-01974-6","DOIUrl":"10.1007/s00011-024-01974-6","url":null,"abstract":"<p><strong>Introduction: </strong>In skin lesions of atopic dermatitis (AD), a chronic inflammatory skin disease, mast cells beyond other immune cells are present in increasing numbers. Upon activation, mast cells release a plethora of mediators, in particular histamine and leukotrienes, as well as chemokines and cytokines, which modulate the immune response of cells in their microenvironment and may influence mast cells in an autocrine loop. This study investigated the effects of histamine and TH2 cytokines on the biosynthesis of cysteinyl leukotrienes (CysLTs) as well as CysLT receptor expression on human mast cells from healthy volunteers and patients with AD.</p><p><strong>Methods: </strong>Human mast cells were generated from CD34+ progenitor cells from peripheral blood. The cultured mast cells were stimulated with IL-4, IL-13, histamine and different histamine receptor selective ligands. Expression of enzymes in the biosynthesis of leukotrienes and expression of CysLT receptors were quantified by real-time PCR. The release of CysLTs was measured by ELISA.</p><p><strong>Results: </strong>Mast cells from AD patients showed higher expression of 5-Lipoxygenase (5-LO) and 5-Lipoxygenase activating protein (FLAP) compared to mast cells from healthy volunteers at baseline and in presence of histamine and TH2 cytokines. Expression of leukotriene C4 synthase (LTC4S), the biosynthesis of CysLTs, and mRNA expression of both CysLT receptors were induced by histamine and TH2 cytokines in mast cells from healthy volunteers and AD patients.</p><p><strong>Conclusion: </strong>We provide evidence that in an acute allergic situation histamine and TH2 cytokines may activate the biosynthesis of pro-allergic cysteinyl leukotrienes and up-regulation of CysLT receptor expression in human mast cells. This suggests a novel mechanism for sustaining mast cell activation through a possible autocrine signalling loop under these conditions.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"32"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074312","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}