Inflammation Research最新文献

{"title":"CUR-PDT induces ferroptosis of RA-FLS via the Nrf2/xCT/GPX4 pathway to inhibit proliferation in rheumatoid arthritis.","authors":"Lihua Sun, Yajuan Niu, Bo Liao, Linlin Liu, Yi Peng, Kaiting Li, Xinhua Chen, Qing Chen, Dingqun Bai","doi":"10.1007/s00011-025-02019-2","DOIUrl":"https://doi.org/10.1007/s00011-025-02019-2","url":null,"abstract":"<p><strong>Objective: </strong>Ferroptosis is a non-apoptotic cell death mechanism driven by reactive oxygen species (ROS) and iron. Its significance in inflammatory arthritis is well-established, but its role in rheumatoid arthritis (RA) remains uncertain. This study aimed to clarify the mechanisms through which curcumin-mediated photodynamic therapy (CUR-PDT) triggers ferroptosis in RA fibroblast-like synoviocytes (FLSs).</p><p><strong>Methods: </strong>In vivo studies using a collagen-induced arthritis (CIA) rat model evaluated CUR-PDT effects on joint edema, synovial inflammation, and fibrosis through paw volume measurements and H&E and Masson's trichrome staining. The expression of Nrf2, xCT, and GPX4 in FLSs was assessed via ELISA and immunohistochemistry. In vitro, MH7A cells treated with TNF-α were analyzed for viability, proliferation, invasion, and migration through various assays. Mitochondrial potential and morphology were examined using JC-1 staining and transmission electron microscopy (TEM). Ferroptosis biomarkers, including ROS, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and Fe²⁺ levels, were measured. Nrf2, xCT, and GPX4 levels were quantified with RT-qPCR, Western blot, and immunofluorescence. Small interfering RNA (siRNA) was employed to knock down Nrf2 to validate the effect of CUR-PDT on ferroptosis in RA-FLS.</p><p><strong>Results: </strong>The CUR-PDT therapy markedly reduced joint inflammation and collagen deposition in the synovial tissue of CIA rats. It effectively alleviated both inflammation and hyperplasia. Moreover, this therapy facilitated ferroptosis within the synovial tissue. In vitro analyses indicated that CUR-PDT diminished the proliferation and viability of FLSs, resulting in increased ROS levels in the cells. This cascade initiated ferroptosis, as evidenced by decreased glutathione, heightened iron concentrations, mitochondrial shrinkage, and reduced mitochondrial membrane potential. Crucially, the expression of xCT and GPX4 was significantly lowered. Interestingly, knocking down the Nrf2 gene amplified this effect, leading to an even greater reduction in xCT and GPX4 expression. In this context, RA-FLSs exhibited more pronounced ferroptotic traits, including diminished proliferation, invasion, and migration.</p><p><strong>Conclusions: </strong>This study elucidated a mechanism by which CUR-PDT triggers ferroptosis in FLSs through the downregulation of the Nrf2-xCT-GPX4 signaling cascade, thereby effectively hindering the progression of RA and emphasizing the importance of targeting Nrf2 in disease advancement.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"53"},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630382","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":"Peroxisome proliferator-activated receptor gamma prevents activation of RBL-2H3 cells by inhibiting FcεRI-mediated signal transduction.","authors":"Yu Zhang, Suyu Ruan, Yuhang Xie, Xiaoqing Rui, Jianjun Zhou, Weihua Wang","doi":"10.1007/s00011-025-02022-7","DOIUrl":"https://doi.org/10.1007/s00011-025-02022-7","url":null,"abstract":"<p><strong>Background: </strong>Mast cells are essential contributors to the pathophysiology of allergic diseases. Peroxisome proliferator-activated receptor gamma (PPAR-γ) has recently been identified as being involved in the anti-inflammatory response by inhibiting mast cell activation.</p><p><strong>Method: </strong>In this study, the PPAR-γ agonist pioglitazone (PIO) was employed to evaluate the effects of PPAR-γ on the degranulation and production of pro-inflammatory mediators in RBL-2H3 cells. Meanwhile, differentially expressed genes (DEGs) were characterised in mast cells exposed to PIO, and pathway enrichment analysis were conducted. Furthermore, we conducted validation to confirm the involvement of PPAR-γ signaling pathways in the FcεRI-mediated signal transduction in mast cells.</p><p><strong>Results: </strong>Administration of PIO significantly reduced the release of β-hexosaminidase and the mRNA expression levels of pro-inflammatory cytokines induced by the cross-linking of FcεRIs expressed on the surface of RBL-2H3 cells. A total of 24 DEGs were identified between RBL-2H3 cells treated with and without PIO, and there were 15 up-regulated and 9 down-regulated. GO and KEGG analyses revealed that the immune system, signal transduction, infectious disease, and signaling molecules and interactions were the most enriched annotations. According to PPI network analysis, most DEGs interacted with PPAR-γ. PPAR-γ agonist could activate PPAR-γ and NRF2 signaling pathways in resting RBL-2H3 cells. The protein expression levels of PPAR-γ, Cpt1a, and Acsl4 were greatly upregulated in activated RBL-2H3 cells mediated by FcεRI aggregation. Moreover, the suppressive effects of PPAR-γ agonist on degranulation and phosphorylation levels of FcεRI-mediated signaling molecules in RBL-2H3 cells were PPAR-γ-dependent.</p><p><strong>Conclusion: </strong>These data demonstrate that PPAR-γ inhibits FcεRI-mediated mast cell activation by modulating intracellular-specific signal transduction in a PPAR-γ-dependent manner.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"49"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584856","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":"Interlukin-23 inhibitors as an induction and maintenance therapy for moderate to severe ulcerative colitis: a systematic review and meta‑analysis of randomized controlled trials.","authors":"Omar Saab, Hasan Al-Obaidi, Marwah Algodi, Asma Algodi, Yasir Rashid, Alhareth Al-Sagban, Hayder Alamily, Nooraldin Merza, Layth Alzubaidy, Andrew DuPont","doi":"10.1007/s00011-025-02017-4","DOIUrl":"https://doi.org/10.1007/s00011-025-02017-4","url":null,"abstract":"<p><strong>Background and objective: </strong>Targeting the interleukin (IL)-23 axis is an emerging treatment target for ulcerative colitis (UC), with several positive randomized controlled trials (RCTs). We aim to investigate the safety and efficacy of IL-23 inhibitors for the induction and maintenance treatment of moderate to severe UC.</p><p><strong>Methods: </strong>A systematic review and meta-analysis synthesizing evidence from RCTs obtained from PubMed, Cochrane, Scopus, and Web of Science from inception to August 2024. We used the fixed-effects model to report dichotomous outcomes using the risk ratio (RR) with a 95% confidence interval (CI).</p><p><strong>Prospero id: </strong>CRD42024589935.</p><p><strong>Results: </strong>Four records, reporting four induction trials and three maintenance trials, with 2,699 patients in the induction phase and 1,015 in the maintenance phase, were included. IL-23 inhibitors significantly increased the rate of clinical remission in the induction phase (RR: 2.19, 95%CI [1.72, 2.78]) and maintenance phase (RR: 1.55, 95%CI [1.26, 1.90]); endoscopic remission in induction phase (RR: 1.76, 95%CI [1.41, 2.18]) and maintenance phase (RR: 1.63, 95%CI [1.21, 1.85]); histo-endoscopic mucosal healing in induction phase (RR: 2.06, 95%CI [1.60, 2.64]) and maintenance phase (RR: 1.48, 95%CI [1.14, 1.90]). Also, IL-23 inhibitors significantly decreased the incidence of serious adverse events in the induction phase (RR: 0.37, 95%CI [0.26, 0.55]) and maintenance phase (RR: 0.53, 95%CI [0.33, 0.83]).</p><p><strong>Conclusion: </strong>IL-23 inhibitors are effective as an induction and maintenance therapy for moderate to severe UC based on the significantly increased rates of clinical, endoscopic, and histological remission. Also, the safety profile of IL-23 inhibitors is favorable, with a significantly decreased incidence of serious adverse events compared to placebo.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"50"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585600","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":"Cxcl9-deficiency attenuates the progression of post-traumatic osteoarthritis in mice.","authors":"Antonia Donat, Weixin Xie, Shan Jiang, Laura Janina Brylka, Thorsten Schinke, Tim Rolvien, Karl-Heinz Frosch, Anke Baranowsky, Johannes Keller","doi":"10.1007/s00011-025-02013-8","DOIUrl":"10.1007/s00011-025-02013-8","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is one of the leading causes of disability in the aging population. While about 10% of the adult population is affected by OA, there is to date no curative treatment and joint replacement surgery remains the only option for treating end-stage OA. Previous studies found elevated levels of the chemokine C-X-C motif ligand 9 (CXCL9) in the synovial fluid of OA knees. However, the exact role of CXCL9 in OA progression is still unknown.</p><p><strong>Methods: </strong>Female wild-type and Cxcl9-deficient mice were challenged with a unilateral anterior cruciate ligament transection (ACLT). Joint destruction in early and late stages of experimental OA was assessed using micro-CT scanning, histological scoring, histomorphometry, and gene expression analysis.</p><p><strong>Results: </strong>Inactivation of Cxcl9 protected from cartilage destruction and osteophyte formation in post-traumatic OA in mice. Similarly, indices of joint inflammation including synovitis and expression of pro-inflammatory interleukin-1beta were reduced in OA knees of Cxcl9-deficient mice. However, bone erosion and pathophysiological changes in the subchondral bone compartment remained unaffected in Cxcl9-deficient mice with experimental OA.</p><p><strong>Conclusion: </strong>Our results point towards a pro-inflammatory role of CXCL9 in OA and identify a potential new target for the pharmacological treatment of OA.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"48"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566964","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":"Decoy oligonucleotides targeting NF-κB: a promising therapeutic approach for inflammatory diseases.","authors":"Maryam Mahjoubin-Tehran, Samaneh Rezaei, Alexandra E Butler, Amirhossein Sahebkar","doi":"10.1007/s00011-025-02021-8","DOIUrl":"https://doi.org/10.1007/s00011-025-02021-8","url":null,"abstract":"<p><p>Nuclear factor-kappa B (NF-κB) transcription factor plays a crucial function in controlling several cellular processes, including the production of inflammatory mediators. The aberrant activation of this transcription factor and its signaling pathway is associated with the pathophysiology of many diseases. Therefore, discovering drugs that target NF-κB is crucial for treating various diseases. Decoy oligonucleotides (decoy ONs) are a pharmacological approach that specifically inhibits NF-κB activation and are used to treat several inflammatory diseases. Decoys that target NF-κB have been shown to enhance radiosensitivity and drug sensitivity in vitro and strongly block IL-6 and IL-8 gene expression induced by TNF-α in experimental cell systems. In vivo, NF-κB decoy reduced atherosclerotic plaque, prevented atopic dermatitis and extended cardiac transplant survival. Decoys have the potential to be used in clinical applications, but they face several challenges. To overcome these limitations, researchers have conducted studies on chemical modifications and delivery techniques. Innovative compounds that target NF-κB, such as NF-κB-decoy-based sensor-containing models, phosphorothioate hairpin-modified oligonucleotides, and peptide nucleic acid (PNA)-based transcription factor decoys, are very attractive. This research aims to explore the use of decoys to combat NF-κB in various disorders.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"47"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566965","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":"The landscape of decidual immune cells at the maternal-fetal interface in parturition and preterm birth.","authors":"Mu Lv, Yuanhui Jia, Jiaqi Dong, Shengyu Wu, Hao Ying","doi":"10.1007/s00011-025-02015-6","DOIUrl":"10.1007/s00011-025-02015-6","url":null,"abstract":"<p><strong>Background: </strong>Parturition is similar to an inflammatory response in which resident and infiltrating immune cells release cytokines and chemokines into the maternal-fetal interface, promoting expulsion of the fetus from the mother. The untimely activation of these inflammatory pathways can result in preterm labor. The maternal-fetal interface is composed mainly of decidual tissue and placental villous space.</p><p><strong>Objective: </strong>The objective of this review is to examine the role and mechanisms of decidual immune cells during parturition and preterm birth. A deeper understanding of decidual immune cells at the maternal-fetal interface could provide significant insight into parturition and preterm birth pathogenesis.</p><p><strong>Methods: </strong>We searched major databases (including PubMed, Web of Science, and Google Scholar etc.) for literature encompassing decidual immune cells, parturition and preterm birth up to July 2024 and combined with studies found in the reference lists of the included studies.</p><p><strong>Results: </strong>Decidual neutrophils release inflammatory mediators that facilitate parturition. The M1/M2 ratio of decidual macrophages increases among preterm birth population. Mast cells may cause uterine contractions. In parturition and preterm birth, there is an increase in CD56^dimCD16⁺ natural killer cells and immature dendritic cells. The increase of Th1/Th2 and Th17/Treg cells leads to preterm birth. Women with preterm birth had a higher proportion of decidual B cells. ILC2 can help protect the steady-state environment at the maternal-fetal interface. The activation of invariant NKT cells plays an important role in inflammation-induced preterm birth. These decidual immune cells communicate with each other. The development of sequencing technology enables a more in-depth study of decidual immune cells.</p><p><strong>Conclusion: </strong>The dynamic balance of the maternal-fetal immune microenvironment plays a crucial role in maintaining human pregnancy and in the initiation of delivery. A deep understanding of the mechanism of decidual immune dysfunction is crucial for understanding the pathogenesis of preterm birth.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"44"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556764","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":"Exploring druggable targets and inflammation-mediated pathways in cancer: a Mendelian randomization analysis integrating transcriptomic and proteomic data.","authors":"Hao Pan, Changqing Jing","doi":"10.1007/s00011-025-02011-w","DOIUrl":"https://doi.org/10.1007/s00011-025-02011-w","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains a predominant global health challenge, necessitating the ongoing exploration of novel biomarkers and therapeutic targets to improve diagnosis and treatment.</p><p><strong>Methods: </strong>By integrating expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) data, we performed Mendelian randomization (MR) analysis to identify potential druggable targets at the gene expression and protein levels for multiple cancers. We conducted mediation analysis to explore whether inflammatory factors mediate the pathways linking identified druggable targets to cancer. Phenome-wide MR analysis, drug prediction, and molecular docking were employed to evaluate the medicinal potential.</p><p><strong>Results: </strong>We finally identified five druggable targets: CDKN1A, FES, and PDIA3 were associated with breast cancer, whereas TP53 and VAMP8 were associated with prostate cancer. Mediation analysis identified six inflammatory proteins as potential mediators in the causal pathways from these druggable targets to cancer: caspase 8, interleukin-1-alpha, C-X-C motif chemokine 1, C-C motif chemokine 23, TNF-related apoptosis-inducing ligand, and interleukin-6. Subsequent analyses further provided evidence supporting the pharmaceutical potential of these five targets.</p><p><strong>Conclusions: </strong>Our study identified five druggable targets causally associated with breast and prostate cancers, with six inflammatory proteins acting as potential mediators, providing novel insights into the treatment of these cancers.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"46"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556762","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":"The relationship between the dynamic trajectory of inflammatory markers in VA-ECMO patients and the 28-day survival rate, as well as mediating causal analysis.","authors":"You Zhou, Zhi Cheng, Liqun Sun, Jiayan Han, Suhui Li, Xin Wang, Leiming Xu","doi":"10.1007/s00011-025-01999-5","DOIUrl":"https://doi.org/10.1007/s00011-025-01999-5","url":null,"abstract":"<p><strong>Background: </strong>Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a simplified cardiopulmonary bypass device that provides temporary respiratory and circulatory support and adequate recovery time for the heart and lung, but the mortality rate of acute and critically ill patients undergoing VA-ECMO is still high. Progression of systemic inflammatory response is associated with mortality in ECMO patients. The objective of this study was to investigate the dynamic changes of various inflammatory markers and their relationship with 28-day mortality in patients with VA-ECMO.</p><p><strong>Methods: </strong>A retrospective cohort analysis was conducted on 200 patients receiving VA-ECMO treatment evaluating inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory response index (SIRI), procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) at various time points. A dynamic trajectory model was constructed, and survival differences between groups were assessed using Kaplan-Meier plots and log-rank tests. Multiple Cox proportional hazard models were built to analyze the relationship between dynamic trajectories and clinical outcomes. Causal mediation analysis was applied to determine whether changes in inflammatory trajectories mediated survival outcomes in patients on VA-ECMO through other variables.</p><p><strong>Results: </strong>Age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Lactic acid, PCO2, aspartate aminotransferase (AST) levels, diastolic blood pressure, mean arterial pressure and pH significantly impacted the 28-day survival rate (p < 0.05), with higher mortality observed in patients exhibiting poor inflammatory trajectories.Kaplan-Meier survival analysis revealed that patients in the ascending (AS) group had a significantly higher risk of death than those in the stable (ST) and descending (DS) groups (log-rank p < 0.001). Furthermore, multivariate Cox regression analysis identified IL-6 as the most strongly correlated inflammatory marker with mortality risk [Hazard ratio (HR) = 1.97, 95% confidence interval (CI) 1.35-2.87, p < 0.001].</p><p><strong>Conclusions: </strong>This study highlights the importance of dynamic monitoring of inflammatory biomarkers in patients on VA-ECMO, suggesting that individualized treatment adjustments based on these markers could enhance survival rates. Future research should prioritize larger, multicenter cohort studies and clinical trials to validate these findings, aiming to optimize treatment strategies for patients on VA-ECMO.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"45"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556775","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":"Exploring macrophage and nerve interaction in endometriosis-associated pain: the inductive role of IL-33.","authors":"Jue Li, Zhijing Wu, Nan Li, Jianhong Wang, Meihua Huang, Li Zhu, Guiping Wan, Zhenzhen Zhang","doi":"10.1007/s00011-025-02010-x","DOIUrl":"https://doi.org/10.1007/s00011-025-02010-x","url":null,"abstract":"<p><p>Endometriosis, a persistent inflammatory disease, is associated with pelvic or abdominal pain. The immune system and sensory nervous system show a synergistic effect on regulation of pain. In particular, Interleukin-33 (IL-33) is released as a danger signal and drives key hallmarks of severe endometriosis. To explore the mechanistic involvement of IL-33 in pain associated with endometriosis, both an in vivo murine endometriosis model and in vitro experiments with RAW 264.7 cells and dorsal root ganglion (DRG) neurons were utilized. In vivo, we demonstrated that IL-33 significantly exacerbated endometriosis and induced hyperalgesia in mice. By interacting with the ST2 receptor in macrophages, IL-33 enhanced the release of tumor necrosis factor α (TNF-α) and Interleukin 1β (IL-1β). This process set off an inflammatory cascade, which further facilitated macrophages recruitment and neurogenesis in ectopic lesions. As an ion channel expressed by nociceptors, transient receptor potential vanilloid 1 (TRPV1) expression was significantly increased in DRG in the presence of IL-33. In vitro, we confirmed that IL-33 elevated the release of TNF-α in macrophages. Ultimately, macrophage-derived TNF-α increased TRPV1 protein level in DRG neuronal cells through the TNFR1/p38 MAPK signaling pathway. Overall, these results revealed an inductive role of IL-33 in pain associated with endometriosis, and highlighted the interaction between macrophages and sensory neurons.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"42"},"PeriodicalIF":4.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448946","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":"Intranasal dupilumab improves responsiveness to steroid in an asthma mouse model.","authors":"Baraa Khalid Salah Al-Sheakly, Fatemeh Saheb Sharif-Askari, Narjes Saheb Sharif-Askari, Adel M Zakri, Bushra Mdkhana, Mariam Wed Abdelaziz Eladham, Jennifer E Hundt, Ibrahim Hachim, Rabih Halwani","doi":"10.1007/s00011-024-01991-5","DOIUrl":"https://doi.org/10.1007/s00011-024-01991-5","url":null,"abstract":"<p><strong>Aims: </strong>The study aimed to evaluate the efficacy of local intranasal delivery of dupilumab, a monoclonal antibody targeting IL-4Rα, in comparison to intraperitoneal delivery in a mouse model of steroid-hyporesponsive asthma, a condition characterized by limited therapeutic options.</p><p><strong>Methods: </strong>Dupilumab was administered via both intranasal and intraperitoneal routes to a mouse model of steroid-hyporesponsive asthma. The efficacy of the treatment was assessed through histological evaluations of inflammation and goblet cell metaplasia, analysis of immune cell infiltration in bronchoalveolar lavage fluid via cytospin, and measurement of total airway resistance using FlexiVent. Additionally, gene and protein expression related to steroid hypo-responsiveness and tissue remodeling were analyzed.</p><p><strong>Results: </strong>Intranasal administration of dupilumab significantly reduced inflammation and goblet cell metaplasia in the bronchial epithelium. It also led to a decrease in immune cell infiltration in bronchoalveolar lavage fluid and reduced total airway resistance. Furthermore, the intranasal dupilumab-treated group exhibited lower expression of genes and proteins associated with steroid hypo-responsiveness and tissue remodeling.</p><p><strong>Conclusions: </strong>Our findings demonstrate that intranasal administration of dupilumab not only effectively reduces inflammation but also significantly reverses steroid hypo-responsiveness and tissue remodeling, outperforming systemic delivery. Thus, local intranasal administration of dupilumab offers superior therapeutic benefits in managing steroid-hyporesponsive asthma.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"43"},"PeriodicalIF":4.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448953","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}