Inflammation最新文献

{"title":"Fibroblast growth factor 10 alleviates LPS-induced acute lung injury by promoting recruited macrophage M2 polarization.","authors":"Nana Feng, Yufan Li, Fengxia Guo, Juan Song, Lu Wang, Miao Li, Kaijing Gao, Xiaocen Wang, Dejie Chu, Yuanlin Song, Linlin Wang","doi":"10.1007/s10753-024-02158-4","DOIUrl":"10.1007/s10753-024-02158-4","url":null,"abstract":"<p><p>Acute lung injury (ALI) is characterized by damage to the alveoli and an overabundance of inflammation. Representing a serious inflammatory condition, ALI lacks a precise treatment approach. Despite the recognized benefit impacts of Fibroblast growth factor-10 (FGF10) on ALI, the underlying mechanisms remain unelucidated. To study the role of FGF10 in ALI, C57BL/6 J mice were intratracheally injected with 5 mg/kg Lipopolysaccharide (LPS) with FGF10 (5 mg/kg) or an equal volume of PBS. Inflammatory factors were quantified in bronchoalveolar lavage fluid (BALF) and plasma using ELISA. RNA sequencing of F4/80⁺Ly6G^- macrophages in BALF explored changes in macrophage phenotype and potential mechanisms. Macrophage polarization in BALF was assessed using qRT-PCR, flow cytometry, and Western blot analysis. In vitro, a Transwell co-culture of mouse lung epithelial cells (MLE12) and bone marrow macrophages (BMDM) validated the role of FGF10 in modulating LPS-induced macrophage phenotypic changes. FGF10 ameliorated LPS-induced ALI by diminishing pro-inflammatory factors (IL-1β, TNF-α, and IL-6) and the neutrophil accumulation in BALF. FGF10 also increased the levels of anti-inflammatory factor IL-10. The FGF10 intervention group exhibited enhanced gene expression of macrophage arginine biosynthesis marker (ARG1), and expression of M2-type marker CD206 in monocytes and macrophages. In addition, phosphorylated STAT3 expression increased in isolated monocyte-derived macrophages. Experiments in vitro confirmed that FGF10 could elevate macrophage M2 marker ARG1 expression through the JAK2/STAT3 pathway. FGF10 ameliorates acute LPS-induced lung injury by modulating the polarization of monocyte-derived macrophages recruited in the alveolar space to the M2 type.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1828-1838"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STC-1 alleviates airway inflammation by regulating epithelial cell apoptosis through the 5-LO pathway.","authors":"Shijia Wang, Zhijian Tu, Chenping Li, Xiao Jin, Zehong Chen, Xiaofei Ye, Shuyao Xu, Jihao Cai, Chang Cai","doi":"10.1007/s10753-024-02181-5","DOIUrl":"10.1007/s10753-024-02181-5","url":null,"abstract":"<p><p>Airway inflammation plays a key role in the pathogenesis and development of asthma. Stanniocalcin-1 (STC-1) has powerful antioxidant, anti-inflammatory and anti-apoptotic functions but its impact on the airway inflammation in asthma lacks evidence. Here, we investigated the effect and potential mechanism of STC-1 on airway inflammation through asthmatic mice model and lipopolysaccharide (LPS)-treated BEAS-2B cells. The data showed that STC-1 treatment before the challenge exerted protective effect on ovalbumin (OVA)-induced asthmatic mice, i.e., decreased the inflammatory cell infiltration, mucus secretion, cytokine levels, apoptosis levels, and p38 MAPK signaling. Additionally, STC-1 reduced 5-LO expression. Meanwhile, STC-1 decreased p38 MAPK signaling, cytokine production, mucin MUC5AC production, 5-LO expression and nuclear translocation, and LTB4 production in vitro. Ultimately, transforming growth factor <math><mi>β</mi></math> (TGF- <math><mi>β</mi></math> ), as a 5-LO inducer, reversed the anti-inflammatory and anti-apoptotic effects of STC-1 in BEAS-2B cells by up-regulating 5-LO expression. It reveals the potential of STC-1 to act as an additional therapy to mitigate airway inflammation in asthma and inhibit 5-LO expression.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2152-2165"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferol Remodels Liver Monocyte Populations and Treats Hepatic Fibrosis in Mice by Modulating Intestinal Flora and Metabolic Reprogramming.","authors":"Zhiqin Zhu, Zhiqi Zhu, Zhenyi Shi, Chen Wang, Fengsheng Chen","doi":"10.1007/s10753-024-02184-2","DOIUrl":"10.1007/s10753-024-02184-2","url":null,"abstract":"<p><p>Changes in gut flora are associated with liver fibrosis. The interactions of host with intestinal flora are still unknown, with little research investigating such interactions with comprehensive multi-omics data. The present work analyzed and integrated large-scale multi-omics transcriptomics, microbiome, metabolome, and single-cell RNA-sequencing datasets from Kaempferol-treated and untreated control groups by advanced bioinformatics methods. This study concludes that kaempferol dose-dependently improved serum markers (like AST, ALT, TBil, Alb, and PT) and suppressed fibrosis markers (including HA, PC III, LN, α-SMA, and Collagen I), while kaempferol also increased body weight. Mechanistically, kaempferol improved the metabolic levels of intestinal flora dysbiosis and associated lipids. This was achieved by increasing the abundance of g__Robinsoniella, g__Erysipelotrichaceae_UCG-003, g__Coriobacteriaceae_UCG-002, and 5-Methylcytidine, all-trans-5,6- Epoxyretinoic acid, LPI (18:0), LPI (20:4), etc. to achieve this. Kaemferol exerts anti-inflammatory and immune-enhancing effects by down-regulating the Th17/IL-17 signaling pathway in PDGF-induced LX2 cells. In addition, kaempferol administration remarkably elevated CD4 + T and CD8 + T cellular proportions, thereby activating immune cells for protecting the body and controlling inflammatory conditions. The combined interaction of multiple data may explain how Kaempferol modulates the intestinal flora thereby remodeling the hepatocyte population and alleviating liver fibrosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2198-2216"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetyl 11-Keto Beta-Boswellic Acid Improves Neurological Functions in a Mouse Model of Multiple Sclerosis.","authors":"Saeed Karima, Seyyed Hossein Khatami, Sajad Ehtiati, Sara Khoshtinatnikkhouy, Reza Ataei Kachouei, Ali Jahanbazi Jahan-Abad, Abbas Tafakhori, Hadis Firoozpour, Farzaneh Salmani","doi":"10.1007/s10753-024-02176-2","DOIUrl":"10.1007/s10753-024-02176-2","url":null,"abstract":"<p><p>Acetyl-11-keto-β-boswellic acid is one of the main active components of Boswellia sp. resin with the most potent anti-inflammatory activity. In recent years, herbal therapy has received considerable attention for the treatments of inflammatory and demyelinating diseases such as Multiple sclerosis (MS). Studies have shown that herbal compounds could enhance myelin repair and suppress inflammation. This study was designed to investigate the therapeutic effects of intraperitoneal administration of AKBA in Experimental Autoimmune Encephalomyelitis (EAE), as an animal model of MS. Following EAE induction in female C57BL/6J mice, animals were treated with AKBA and the levels of different serum inflammatory mediators, as well as motor functions, myelination, and inflammatory cell infiltration were assessed. Our results revealed that the application of AKBA alleviated EAE clinical severity, and suppressed inflammation, demyelination, leukocyte infiltration, and gliosis in EAE mice. Our findings suggest that the therapeutic effects of AKBA are likely a consequence of its neuroprotective and anti-inflammatory properties. The beneficial effects of AKBA may therefore provide new insights in various neuroinflammatory diseases such as MS and thereby could serve as a potential treatment candidate.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2078-2086"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Risk Factors for Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Retrospective Study.","authors":"Min Feng, Fanxing Meng, Yuhan Jia, Yanlin Wang, Guozhen Ji, Chong Gao, Jing Luo","doi":"10.1007/s10753-024-02157-5","DOIUrl":"10.1007/s10753-024-02157-5","url":null,"abstract":"<p><strong>Objective: </strong>Patients with rheumatoid arthritis (RA) have increased mortality and morbidity rates owing to cardiovascular diseases (CVD). Timely detection of CVD in RA can greatly improve patient prognosis; however, this technique remains challenging. We aimed to investigate the risk factors for CVD incidence in patients with RA.</p><p><strong>Methods: </strong>This retrospective study included RA patients without CVD risk factors (n = 402), RA with CVD risk factors (n = 394), and RA with CVD (n = 201). Their data on routine examination indicators, vascular endothelial growth factor (VEGF), and immune cells were obtained from medical records. The characteristic variables between each group were screened using univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and logistic regression (LR) models, and individualized nomograms were further established to more conveniently observe the likelihood of CVD in RA.</p><p><strong>Results: </strong>Univariate analysis revealed significantly elevated levels of white blood cells (WBC), blood urea nitrogen (BUN), creatinine, creatine kinase (CK), lactate dehydrogenase (LDH), VEGF, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), apolipoprotein B100 (ApoB100), and apolipoprotein E (ApoE) in RA patients with CVD, whereas apolipoprotein A1 (ApoA1) and high-density lipoprotein/cholesterol (HDL/TC) were decreased. Furthermore, the ratio of regulatory T (Treg) cells exhibiting excellent separation performance in RA patients with CVD was significantly lower than that in other groups, whereas the ratios of Th1/Th2/NK and Treg cells were significantly elevated. The LASSO, RF, and LR models were also used to identify the risk factors for CVD in patients with RA. Through the final selected indicators screened using the three machine learning models and univariate analysis, a convenient nomogram was established to observe the likelihood of CVD in patients with RA.</p><p><strong>Conclusions: </strong>Serum lipids, lipoproteins, and reduction of Treg cells have been identified as risk factors for CVD in patients with RA. Three nomograms combining various risk factors were constructed to predict CVD occurring in patients with RA (RA with/without CVD risk factors).</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1811-1827"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin-1 Facilitates Macrophage M1 Polarization by Enhancing Glycolysis Through the Activation of HIF1α in Lipopolysaccharide-Induced Acute Kidney Injury.","authors":"Ru-Xue Diao, Wu-Yang Lv, Yu-Chen Wang, Qiu-Ling Shen, Kai-Hong Tang, Xiao-Xiao Luo, Ying-Yu Jin","doi":"10.1007/s10753-024-02154-8","DOIUrl":"10.1007/s10753-024-02154-8","url":null,"abstract":"<p><p>This study aimed to investigate how aquaporin 1 (AQP1) modulates hypoxia-inducible factor-1α (HIF1α) to promote glycolysis and drive the M1 polarization of macrophages. Within 12 h post-treatment with LPS to induce acute kidney injury in rats, a significant upregulation of AQP1 and HIF1α protein levels was noted in serum and kidney tissues. This elevation corresponded with a decrease in blood glucose concentrations and an enhancement of glycolytic activity relative to the control group. Furthermore, there was a pronounced reduction in the circulating levels of the anti-inflammatory cytokine IL-10, accompanied by an upregulation in the levels of the pro-inflammatory cytokines IL-6 and TNF-α. The administration of an HIF1α inhibitor reversed these effects, which did not affect the production of AQP1 protein. In cellular assays, AQP1 knockdown mitigated the increase in HIF1α expression induced by LPS. Furthermore, the suppression of HIF1α with PX-478 led to decreased expression levels of Hexokinase 2 (HK2) and Lactate Dehydrogenase A (LDHA), indicating that AQP1 regulates glycolysis through HIF1α. M1 polarization of macrophages was reduced by AQP1 knockdown and was further diminished by the addition of an HIF1α inhibitor. Inhibition of the glycolytic process not only weakened M1 polarization but also promoted M2 polarization, thereby reducing the release of inflammatory cytokines. These findings provide a novel perspective for developing therapeutic strategies that target AQP1 and HIF1α, potentially improving the treatment of sepsis-associated AKI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1775-1790"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP30-AS1 Suppresses Colon Cancer Cell Inflammatory Response Through NF-κB/MYBBP1A Signaling.","authors":"Ruonan Wang, Xiaolin Li, Yapei Jiang, Haowei Zhang, Shiyue Yang, Weidong Xie, Naihan Xu","doi":"10.1007/s10753-024-02170-8","DOIUrl":"10.1007/s10753-024-02170-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and poses a significant threat to human health. Recent studies have underscored the crucial role of aberrant expression of long non-coding RNAs (lncRNAs) in the initiation and progression of CRC. In this study we identified that lncRNA USP30-AS1 is significantly downregulated in colorectal cancer tissues, particularly in the advanced stages of the disease. This downregulation correlates with reduced survival rates among patients. Enrichment analysis of genes associated with USP30-AS1 indicates a strong association with inflammatory responses. Notably, pro-inflammatory stimuli, including lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α), were found to upregulate the expression of USP30-AS1. Functional assays demonstrated that the knockdown of USP30-AS1 resulted in increased degradation of IκBα protein and enhanced NF-κB transcriptional activity, as well as elevated expression levels of NF-κB downstream inflammatory molecules, including NLRP3, IL-1β, and IL-18. Conversely, ectopic expression of USP30-AS1 inhibited NF-κB transactivation. Mechanistically, USP30-AS1 interacts with MYBBP1A, a known regulator of NF-κB signaling. Notably, overexpression of MYBBP1A alleviated the stimulatory effect of USP30-AS1 knockdown on NF-κB activation. Collectively, these findings suggest that USP30-AS1 acts as a suppressor of colorectal cancer cell growth by modulating the MYBBP1A/NF-κB signaling pathway, thereby highlighting USP30-AS1 as a potential novel therapeutic target for colorectal cancer treatment.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1998-2008"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-6 Exacerbates Oxidative Damage of RPE Cells by Indirectly Destabilizing the mRNA of DNA Repair Genes.","authors":"Huirong Long, Yucong Xiong, Haiyu Liu, Meiling Yang, Ting Liu, Chaoju Gong, Suyan Li","doi":"10.1007/s10753-024-02192-2","DOIUrl":"10.1007/s10753-024-02192-2","url":null,"abstract":"<p><p>Chronic inflammation has been associated with the progression of age-related macular degeneration (AMD) and diabetic retinopathy (DR), and the levels of various inflammatory factors are significantly increased in intraocular fluids of patients with AMD and DR. Therefore, elucidating the roles of inflammatory factors in the oxidative damage of RPE cells will help uncover the pathogenesis of AMD and DR. We have previously demonstrated that E2F1 plays an important role in the antioxidant capacity of RPE cells. Here, our transcriptome analysis shows that E2F1 affected the expressions of DNA repair genes in RPE cells. In addition, we found that E2F1 transactivated the splicing factor SRSF1. SRSF1 knockdown promoted DNA oxidative damage and apoptosis and decreased the mRNA stability of DNA repair genes XRCC2, POLK and LIG4 in RPE cells. Moreover, we found that SRSF1 could bind to the RNA stabilizing factor MATR3, and knockdown of the latter affected the mRNA stability of these DNA repair genes. Notably, interleukin-6 (IL-6), an inflammatory factor upregulated in intraocular fluids of patients with AMD and DR, decreased SRSF1 expression by inducing acetylation of E2F1 at the K125 position. Consistently, SRSF1 overexpression relieved IL-6-induced DNA oxidative damage and apoptosis in RPE cells. In vivo experiment results also confirmed that IL-6 could aggravate retinal oxidative damage. In conclusion, high levels of IL-6 in the eyes of patients with AMD and DR destabilize the mRNAs of DNA repair genes by disrupting the expression of SRSF1, leading to abnormal repair of DNA oxidative damage in RPE cells.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2323-2340"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KW-2449 Ameliorates Cardiac Dysfunction in a Rat Model of Sepsis-Induced Cardiomyopathy.","authors":"Jie Chen, Wei-Jian Zhang, Xiao-Yu Liu, Tian-Peng Hu, Nan Gao, Zhong-Hao Li, Yu Wang, Guo-Qiang Zhang","doi":"10.1007/s10753-024-02223-y","DOIUrl":"10.1007/s10753-024-02223-y","url":null,"abstract":"<p><p>KW-2449 is a novel multitargeted kinase inhibitor that has been reported to alleviate chronic inflammation and altered immunity during the treatment of autoimmune diseases. The aim of the study was to investigate the effect of KW-2449 on sepsis-induced cardiomyopathy (SIC). A rat model of moderate SIC was induced using the cecal ligation and puncture (CLP) method. KW-2449 was administered to rats at 10 mg/kg for 3 consecutive days by intraperitoneal injection. At 24 hours after CLP, echocardiography, electrocardiogram, and hemodynamic analyses were performed. Blood and cardiac tissues were collected for further analysis. RNA sequencing (RNA-seq) analyses were used to identify the key genes affected by KW-2449 treatment during SIC. KW-2449 improved the liver dysfunction in septic rats. KW-2449 significantly improved left ventricular (LV) systolic function and hemodynamics compared to the CLP group. KW-2449 suppressed the systemic inflammatory response, decreased myocardial inflammation and cell apoptosis in the CLP rats. RNA-seq analyses indicated that there were a total of 2256 differentially expressed genes in the CLP group compared to the Control group, among which 63 genes were down-regulated and 59 genes were up-regulated by KW-2449. Specifically, Pparα was identified as a key target gene of KW-2449 in the treatment of SIC by RNA-seq analysis.KW-2449 also significantly upregulated the protein expression of Pparα in the LV tissue of septic rats. KW-2449 reduced systemic inflammation, cardiac inflammation, and improved cardiac dysfunction in the CLP-induced SIC rat model. The underlying mechanism of the cardio-protective role of KW-2449 in the CLP-induced SIC might be related to Pparα.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2732-2744"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting NLRP3 Inflammasome Activation to Alleviate Retinal Inflammation and Protect the Optic Nerve of OPTN(E50K)Mice.","authors":"Shujing Wang, Rong Xiao, Yanfei Lu, Yanfeng Zhang, Shiqi Zhang, Xinna Liu, Huiping Yuan","doi":"10.1007/s10753-024-02178-0","DOIUrl":"10.1007/s10753-024-02178-0","url":null,"abstract":"<p><p>OPTN (E50K) mutation is one of the significant pathogenic mutations in normal tension glaucoma (NTG). The molecular mechanism of NTG optic nerve injury is complex and diverse; its key mechanism is still unclear. The NLR family pyrin domain containing (NLRP3) inflammasome plays an essential role in the occurrence and development of inflammation. There is no report on whether NLRP3 inflammasome activation plays a crucial role in NTG optic nerve injury. Here, we explored the role of retinal inflammatory cascade reaction triggered by NLRP3 inflammasome activation in OPTN (E50K) mutated NTG optic nerve injury. This research may provide innovative strategies for effectively treating NTG optic nerve injury caused by OPTN (E50K) mutation. The R28 cell was constructed by AAV2 transfection, named GFP-R28, WT-R28, and E50K-R28 groups. Western blot, qPCR, and immunofluorescence were performed to measure the expression levels of the neurotrophic factors, the senescence indicators, the NLRP3-related indicators, the expression of the glial cell markers, and the inflammatory cytokines. Further, observe the changes in the above indicators in the WT-R28 and E50K-R28 groups after treatment with MCC950. Next, we compared the expression of neurotrophic factors and senescence indicators, NLRP3-related indicators, glial cell markers, and inflammatory factors between young and old WT and OPTN (E50K) mice. We examined the visual function of mice on days 1, 4 and 7. Furthermore, we observed the retinal morphology and the expression of neurotrophic factors and senescence indicators, NLRP3-related indicators, glial cell markers, and inflammatory factors between all groups were measured. We found that OPTN (E50K) mutations lead to NLRP3 inflammasome activation. The OPTN (E50K) mutant groups showed an inflammatory cascade, including glial cell activation and release of proinflammatory factors, leading to retinal structural and functional impairment in mice.MCC950 effectively inhibited the activation of the NLRP3 inflammasome and alleviated the retinal inflammatory cascade caused by the OPTN (E50K) mutation, ultimately improving visual function and retinal damage in mice. OPTN (E50K) mutation induces the activation of the NLRP3 inflammasome, which leads to a retinal inflammatory cascade. MCC950 can inhibit the activation of the NLRP3 inflammasome and retinal inflammatory cascade, improving visual function in OPTN (E50K) mutation mice.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2105-2121"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}