ImmunoTargets and Therapy最新文献

{"title":"Circulating miR-148a-3p Correlates with Inadequate Induction Response in Pediatric Hodgkin Lymphoma.","authors":"Marius Rohde, Vijay Kumar Singh, Andrea Wolfermann, Birgit Burkhardt, Claudia Blattmann, Daniel Steinbach, Dominik T Schneider, Martin Ebinger, Britta Maecker-Kolhoff, Matthias Braun, Lars Kurch, Christine Mauz-Körholz, Dieter Körholz","doi":"10.2147/ITT.S577426","DOIUrl":"10.2147/ITT.S577426","url":null,"abstract":"<p><p>Pediatric Hodgkin lymphoma (HL) is highly curable, and reducing the treatment intensity in patients who respond well to induction therapy is a key strategy for minimizing long-term adverse effects. Biomarkers that identify good responders at diagnosis would enable further de-escalation of the treatment. Circulating microRNAs (miRNAs) have shown promise as noninvasive indicators of therapeutic response in hematological cancers, yet their association with early metabolic response on quantitative 18F-Fluorodeoxyglucose-Positron Emission Tomography (18F-FDG-PET) in pediatric HL has not been defined. Here, we investigated the potential of circulating miRNAs to predict the response to induction therapy in pediatric HL. Small RNA sequencing of serum samples from 35 patients revealed 24 Hodgkin lymphoma-associated miRNAs that were differentially expressed between adequate and inadequate responders. Subsequent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation demonstrated significantly elevated miR‑148a‑3p levels at diagnosis in inadequate responders to induction therapy than in adequate responders (p=0.009). These results indicate that circulating miR‑148a‑3p may enhance current predictive approaches by identifying high‑risk patients less likely to achieve rapid metabolic remission.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"577426"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Clinical and Electrophysiological Profiles of Chronic Inflammatory Demyelinating Polyneuropathy in Patients with and without Diabetes Mellitus: An Observational Study.","authors":"Abdullah Al Mamun, Most Samsun Nahar Sumi, Mohammad Enayet Hussain, A F M Al Masum Khan, Mohammad Aftab Rassel, Ghulam Kawnayn, Md Abdullah Yusuf, Redoy Ranjan, Adneen Moureen, Dipannita Adhikary, Md Badrul Alam, Quazi Deen Mohammad, Md Nazmul Karim","doi":"10.2147/ITT.S592658","DOIUrl":"10.2147/ITT.S592658","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated, treatable neuropathy with clinical and electrophysiological features that overlap with diabetic polyneuropathy, complicating diagnosis and delaying immunotherapy. This study compared the clinical and electrophysiological characteristics of CIDP in patients with and without diabetes mellitus (DM) to determine whether diabetes modifies disease presentation or severity.</p><p><strong>Methods: </strong>This cross-sectional comparative study was conducted at the National Institute of Neurosciences and Hospital, Dhaka, Bangladesh, from January 2018 to December 2023. Consecutive patients aged ≥15 years with CIDP diagnosed per EFNS/PNS 2010 criteria and reclassified using 2021 EAN/PNS guidelines were enrolled and stratified into CIDP+DM and CIDP-DM groups. Clinical data, disability scores (MRCSS, I-RODS, INCAT), and electrophysiological parameters were compared using Mann-Whitney U and chi-square tests.</p><p><strong>Results: </strong>Of 143 patients (21 CIDP+DM; 122 CIDP-DM), those with diabetes were older at symptom onset (median 55 vs 45 years, p = 0.034) and demonstrated significantly greater distal muscle weakness (p = 0.045), though overall disability scores were comparable. Electrophysiological assessment confirmed demyelination in both groups; however, CIDP+DM patients exhibited more pronounced axonal involvement, evidenced by reduced median and ulnar compound muscle action potential amplitudes (p = 0.034-0.046) and increased tibial F-wave abnormalities (p = 0.042). In age- and sex-adjusted multivariable analyses, diabetes independently modified CIDP by reducing distal muscle power (β = -1.13; p < 0.001), median CMAP at elbow (β = -1.32 mV; p = 0.0006), ulnar CMAP at wrist (β = -1.97 mV; p = 0.0004) and elbow (β = -1.55 mV; p < 0.001), tibial F-wave presence (β = -0.46; p = 0.0002), and overall function with lower MRCSS (β = -3.20; p = 0.04) and higher INCAT scores (β = 1.81; p = 0.004).</p><p><strong>Conclusion: </strong>Diabetes modifies CIDP, producing a mixed demyelinating-axonal phenotype with greater distal motor impairment.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"592658"},"PeriodicalIF":4.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress on Potential Therapeutic Targets for Sepsis-Related Cardiac Dysfunction: From Basic Research to Clinical Translation.","authors":"Yan Gao, Rui Dai, Chang Kong, Zejun Niu, Li Yuan, Xiaojie Liu","doi":"10.2147/ITT.S580700","DOIUrl":"10.2147/ITT.S580700","url":null,"abstract":"<p><p>Sepsis-related cardiac dysfunction (SRCD) is a severe complication of sepsis with complex pathophysiology involving dysregulated inflammatory responses, immune cell dysfunction, and multiple forms of programmed cell death. The review addresses the core pathophysiological mechanisms of SRCD, the central role of immune cell crosstalk (particularly between macrophages and neutrophils), and the evaluation of multi-target therapeutic strategies with an emphasis on natural compounds. We highlight promising interventions, including ginsenosides and melatonin, which exert multi-target protective effects. Future research should integrate insights across these themes to accelerate the development of precise therapies and improve patient survival and quality of life.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"580700"},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of PD-L1 in Lung Cancer: From Biology to Clinical Application.","authors":"Hassan Lamghari, Mehdi Karkouri","doi":"10.2147/ITT.S591588","DOIUrl":"10.2147/ITT.S591588","url":null,"abstract":"<p><p>Lung cancer remains the primary cause of cancer-related mortality worldwide and is mainly classified into non-small cell lung cancer, which accounts for approximately 85% of cases, and small cell lung cancer, representing about 15%. In recent years, major therapeutic progress has been achieved through the development of immunotherapies, particularly immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. These treatments aim to restore antitumor immune responses by blocking the interaction between PD-1, expressed on T lymphocytes, and its ligand PD-L1, which can be overexpressed by tumor cells. Under physiological conditions, PD-L1 plays an essential role in maintaining immune tolerance; however, its dysregulated expression in cancer contributes to immune evasion. The level of PD-L1 expression assessed by immunohistochemistry has emerged as a key predictive biomarker for patient response to immunotherapy. Nevertheless, PD-L1 expression is heterogeneous and influenced by multiple biological, clinical and technical factors. In this review, we aim to summarize the biological role of PD-L1 in lung cancer, discuss its expression patterns and regulatory mechanisms, describe current assessment methods, and highlight its clinical relevance in guiding immunotherapy strategies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"591588"},"PeriodicalIF":4.1,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kasugamycin Inhibits Melanoma Lung Metastasis and CHI3L1-Driven M2-Like Tumor-Associated Macrophage Differentiation.","authors":"Takayuki Sadanaga, Han-Seok Jeong, Roberto Cortez, Joyce H Lee, Suchitra Kamle, Bing Ma, Sung Jae Shin, Jack A Elias, Chun Geun Lee","doi":"10.2147/ITT.S563951","DOIUrl":"10.2147/ITT.S563951","url":null,"abstract":"<p><strong>Purpose: </strong>Chitinase-3-like-1 (CHI3L1) is a potent immune modulator implicated in tumor progression and immune suppression, including melanoma lung metastasis. Kasugamycin (KSM) has been reported as a pan-chitinase inhibitor with antifibrotic activity, but its effects on CHI3L1-driven immune regulation remain poorly defined. This study aimed to determine whether KSM suppresses CHI3L1-mediated tumor progression by modulating tumor-associated macrophage (TAM) differentiation and to elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The anti-tumor effects of KSM were evaluated using a B16/F10 melanoma lung metastasis model. CHI3L1 gain-of-function approaches were used to assess specificity. Lung immune populations were analyzed by flow cytometry. Human THP-1 monocytes were used to examine CHI3L1-induced macrophage differentiation in vitro. Bulk RNA sequencing was performed on differentiated macrophages to identify downstream signaling pathways. Pharmacologic inhibition studies were conducted using the epidermal growth factor receptor (EGFR) inhibitor gefitinib to validate mechanistic links.</p><p><strong>Results: </strong>KSM treatment significantly reduced melanoma lung metastasis in a dose-dependent manner. CHI3L1 overexpression enhanced melanoma lung colony formation, which was effectively abrogated by KSM, indicating CHI3L1-specific anti-tumor activity. In melanoma-challenged lungs, KSM markedly decreased M2-like macrophages expressing CD206, CD163, and PD-L1. In vitro, CHI3L1 promoted M2 macrophage differentiation in THP-1 cells, which was strongly suppressed by KSM. Transcriptomic analysis revealed that EGFR expression was robustly induced by CHI3L1 and counter-regulated by KSM. Inhibition of EGFR signaling with gefitinib significantly attenuated CHI3L1-driven STAT3 activation and M2 macrophage polarization.</p><p><strong>Conclusion: </strong>These findings identify a previously unrecognized anti-tumor mechanism of KSM through inhibition of CHI3L1-EGFR-STAT3 signaling and suppression of M2-like TAM differentiation. KSM may therefore represent a promising immunomodulatory strategy for treating melanoma lung metastasis and other CHI3L1-driven malignancies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"563951"},"PeriodicalIF":4.1,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NUP85 as a Pan-Cancer Immune Biomarker: Integrated Multi Omics and Functional Analyses Reveal Its Role in Tumor Prognosis.","authors":"Weihao Kong, Ying Hu, Kangjie Zhang, Zhipeng Zhu, Yajun Zou, Long Teng, Xingyu Wang, Jianlin Zhang","doi":"10.2147/ITT.S541852","DOIUrl":"10.2147/ITT.S541852","url":null,"abstract":"<p><strong>Purpose: </strong>NUP85 encodes protein components of the Nup107-160 subunit of the nuclear pore complex, belonging to the Nucleoporins (NUPs) family, potentially implicating its role in human cancer. This study aims to elucidate the potential involvement of NUP85 in cancer pathogenesis.</p><p><strong>Methods: </strong>Leveraging data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), CellMiner, and GeneMANIA databases, we investigated the role of NUP85 across various tumors. Correlations between NUP85 expression and pathological stage, histological grade, survival, immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), drug resistance, DNA methylation, copy number variation (CNV), and single-cell expression were analyzed. Gene functional enrichment analysis was conducted to explore NUP85-associated pathways. Molecular biology experiments including Western blotting, flow cytometry, trans-well migration, and invasion assays were performed to validate NUP85's oncogenic role in lung adenocarcinoma (LUAD) and oral squamous cell carcinoma (OSCC) cell lines.</p><p><strong>Results: </strong>Our findings reveal up-regulated expression of NUP85 in most tumor tissues, with significant correlations observed with pathological stage, survival, immune infiltration, TMB, MSI, drug resistance, DNA methylation, and CNV. Molecular biology experiments confirm NUP85's tumor-promoting role in LUAD and OSCC cell lines. Single-cell sequencing data suggest elevated NUP85 expression primarily in proliferative T cells (Tprolif).</p><p><strong>Conclusion: </strong>NUP85 emerges as a potential tumor marker associated with tumor immunity and poor prognosis. These insights offer avenues for the development of novel therapeutic targets and anti-neoplastic drugs.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"541852"},"PeriodicalIF":4.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Conjugation of Antibodies to Heat Shock Protein 70 Activates Immune Responses Against Tumor Cells.","authors":"Mohammad Khosravi, Arezoo Rajaei, Babak Mohammadian, Masoudreza Seyfi Abad Shapouri","doi":"10.2147/ITT.S565942","DOIUrl":"10.2147/ITT.S565942","url":null,"abstract":"<p><strong>Purpose: </strong>The heat shock proteins (HSPs) of <i>Mycobacterium</i> have been identified as immunogenic antigens with chaperone functions. This study evaluated a method to enhance host immune responses against cancer cells by utilizing commercial antibodies conjugated with HSP70 derived from <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i>.</p><p><strong>Methods: </strong>Recombinant HSP70, in conjugation with the monoclonal antibodies trastuzumab and bevacizumab, was employed for both in vivo and in vitro treatment of tumor cells. The cytotoxicity of the antibody-HSP70 complex was assessed on the MCF-7, LS174T, and HEK293T cell lines, after characterization of the cells for expression of the targets. The stimulation of complement activation pathways was examined using a complement fixation assay. The in vivo effects of the HSP70- antibodies were evaluated against xenograft LS174T and MCF-7 tumors in mice. The tumor tissues were evaluated through histopathological analysis.</p><p><strong>Results: </strong>The cytotoxic effect of the antibody-HSP70 complex was significantly greater than that of other treatments against the MCF-7 and LS174T cell lines; this effect was confirmed in the presence of human plasma and leukocyte samples. Additionally, activation of the classical complement pathway has been demonstrated using HSP70 antibodies. Treatment of xenograft tumors with the antibody-HSP70 complex significantly reduced both tumor weight and growth rate, as well as decreased the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1). Histopathological analysis, along with the observed therapeutic efficacy, confirmed the safety of this approach.</p><p><strong>Conclusion: </strong>Overall, stimulating the immune system against cancer cells by targeting innate immune responses could enhance the effectiveness of targeted therapies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"565942"},"PeriodicalIF":4.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.","authors":"Giulia Gualtiero, Helena Buso, Eva C Coopmans, Cinzia Milito, Davide Firinu, Virgil A S H Dalm, Francesco Cinetto","doi":"10.2147/ITT.S582718","DOIUrl":"10.2147/ITT.S582718","url":null,"abstract":"<p><p>Lymphoproliferation represents a common and clinically relevant feature across many Inborn Errors of Immunity (IEIs), reflecting the underlying immune dysregulation that characterizes these disorders. In affected individuals, lymphoproliferation may manifest along a broad clinical spectrum, ranging from benign forms such as lymphadenopathy, splenomegaly, and hepatomegaly to malignant transformation, including lymphoma and leukemia. Multiple and heterogeneous pathogenetic mechanisms contribute to lymphoproliferation in IEIs; however, they can be conceptually grouped into two major categories: excessive lymphocyte activation and proliferation, and defective control of proliferation. The association of lymphoproliferation with autoimmune cytopenia classically defined the Autoimmune Lymphoproliferative Syndrome (ALPS), caused by an impairment in FAS-mediated apoptosis. However, a growing number of IEIs present with overlapping autoimmune lymphoproliferative phenotypes driven by diverse monogenic defects or, in many cases, without an identifiable genetic cause. This expanding spectrum has led to the concept of autoimmune lymphoproliferative immunodeficiencies (ALPID), encompassing a continuum of disorders characterized by lymphoproliferation, autoimmunity and diverse genetic backgrounds, requiring disease-specific therapeutic approaches. This narrative review provides an overview of the main IEIs associated with lymphoproliferation focusing on pathogenic pathways, diagnostic evaluation and classification, and current and emerging targeted therapeutic approaches.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"582718"},"PeriodicalIF":4.1,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Glioblastoma and the Tumor Immune Landscape: Emerging Immunotherapeutic Strategies.","authors":"Zixuan Cao, Shurong Tong, Zihan Wang, Chenhui Ji, Chaoyong Zhang, Xingliang Dai, Bingshan Wu","doi":"10.2147/ITT.S581012","DOIUrl":"10.2147/ITT.S581012","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive malignant tumor affecting the central nervous system. Current standard of care provides only modest clinical benefits, most patients eventually develop tumor recurrence, at which point therapeutic options become markedly restricted and the prognosis remains dismal. In recent years, immunotherapy has achieved significant clinical success in several solid tumors and has become a key strategy for advanced cancers owing to its specificity and potent antitumor activity. Nevertheless, the immunosuppressive tumor microenvironment of recurrent GBM (rGBM), along with its pronounced heterogeneity, and the presence of blood-brain barrier collectively undermine the efficacy of immunotherapy. With increasing insights into the tumor microenvironment and immune escape mechanisms, alongside refinements in immunotherapeutic strategies, immunotherapy may ultimately become one of the therapeutic options for patients with rGBM. Currently, principal immunotherapies under investigation for rGBM include immune checkpoint inhibitors, CAR-T cell therapy, oncolytic virotherapy, and cancer vaccines. In this review, we comprehensively summarize the clinical evidence for these approaches, highlight their mechanisms of action, and critically evaluate the key challenges that limit clinical translation. By integrating recent therapeutic progress and unresolved obstacles, we aim to provide a timely perspective on the optimization of immunotherapy in rGBM and to inform the rational design of future clinical trials.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"581012"},"PeriodicalIF":4.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12970017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UVB Upregulates Inflammatory Cytokines in Rosacea Cell Model by Promoting the Expression of TRPVs and TLR2.","authors":"Yuming Xie, Yue Hu, Junke Huang, Juan Liu, Qing Zhang","doi":"10.2147/ITT.S571037","DOIUrl":"10.2147/ITT.S571037","url":null,"abstract":"<p><strong>Background: </strong>The expression of transient receptor potential vanilloid (TRPV) and Toll-like receptor 2 (TLR2) in the lesion sites of patients with rosacea is increased. Ultraviolet B (UVB) radiation can induce inflammation of keratinocytes in patients with rosacea, but the relationships between UVB and TRPVs/TLR2 in rosacea remain unclear.</p><p><strong>Methods: </strong>RT-qPCR and Western Blot were applied to determine the expression levels of TRPV1, TRPV2, TRPV3, TRPV4 and TLR2 in the rosacea keratinocyte model after ultraviolet irradiation (n=3). After treating the rosacea cell model with TRPV1, TRPV4 and TLR2 inhibitors, ELISA was used to detect the expressions of rosacea-associated inflammatory cytokines in rosacea cells exposed to UVB, including IL-1β, IL-6, IL-8 and TNF-α (n=6). The changes in DNA methylation levels of TRPV1, TRPV4 and TLR2 promoters were detected by MeDIP, and the levels of histone modifications H3K4me3, H3K9me3 and H3K27me3 were determined by ChIP (n=3).</p><p><strong>Results: </strong>UVB exposure increases the secretion levels of rosacea-associated inflammatory cytokines in HaCaT cells and LL-37-induced rosacea keratinocyte models, and promotes the expression of TRPV1, TRPV4 and TLR2 at mRNA and protein levels (P < 0.05). In the LL-37-induced HaCaT cell model, TRPV1 and TLR2 antagonists reduced the secretion levels of IL-1β and IL-8, and TRPV4 antagonists reduced IL-6 secretion level (P < 0.05). Under UVB exposure, TRPV4 and TLR2 antagonists respectively reduced the concentrations of IL-1β and TNF-α in the HaCaT cells stimulated by LL-37 (P < 0.05). In addition, UVB exposure increased the H3K4me3 level of the TRPV1 promoter region in HaCaT cells treated by LL-37 (P < 0.05).</p><p><strong>Conclusion: </strong>Our results indicate that UVB induces inflammatory cytokines in rosacea keratinocyte models through upregulation of TRPV1, TRPV4, and TLR2 expression, potentially mediated by epigenetic mechanisms.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"571037"},"PeriodicalIF":4.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}