Inflammation最新文献_第10页

FDA-Approved Secukinumab Alleviates Glial Activation and Immune Cell Infiltration in MPTP-Induced Mouse Model of Parkinson's Disease. fda批准的Secukinumab减轻mptp诱导的帕金森病小鼠模型中的神经胶质活化和免疫细胞浸润

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-26 DOI: 10.1007/s10753-025-02267-8

Qi Li, Xiaoxuan Han, Mengmeng Dong, Lipeng Bai, Wei Zhang, Wei Liu, Fei Wang, Xiaodong Zhu

{"title":"FDA-Approved Secukinumab Alleviates Glial Activation and Immune Cell Infiltration in MPTP-Induced Mouse Model of Parkinson's Disease.","authors":"Qi Li, Xiaoxuan Han, Mengmeng Dong, Lipeng Bai, Wei Zhang, Wei Liu, Fei Wang, Xiaodong Zhu","doi":"10.1007/s10753-025-02267-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02267-8","url":null,"abstract":"Interleukin-17A (IL-17A) has been implicated in the progression of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the effect of the FDA-approved Secukinumab (SEC), an IL-17A inhibitor, on PD remains unclear. This study aimed to investigate the neuroprotective effect of SEC and its potential mechanisms in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Male C57BL/6 J mice were mainly assigned to three groups: Sham, MPTP, and MPTP + SEC. Motor coordination was assessed using the climbing rod and rotarod tests. Dopaminergic neurons (TH +) and glial cells (Iba-1 + , GFAP +) in the substantia nigra were evaluated using immunohistochemistry and immunofluorescence. Flow cytometry was used to analyze immune cell populations in the brain and spleen. Inflammatory cytokines and chemokines were quantified using RT-PCR. SEC treatment significantly alleviated the loss of dopaminergic neurons and improved motor coordination in MPTP mice. It also reduced the infiltration of peripheral immune cells, including CD4 + T cells, NK cells, and monocyte-macrophages into the brain. SEC attenuated glial activation (Iba-1 + , GFAP +) and decreased the expression of pro-inflammatory cytokines and chemokines (CCL2, CXCL9), which recruit immune cells into the brain. These results suggest that Secukinumab protects dopaminergic neurons and attenuates neuroinflammation in MPTP-induced model. SEC treatment in PD might be an effective therapeutic approach for clinical application in the future. HIGHLIGHTS: • Secukinumab reduces the loss of dopaminergic neurons and axons in MPTP mice. • Secukinumab inhibits the infiltration of peripheral immune cells into the brain in MPTP mice. • Secukinumab inhibits the activation of glial cells and reduces neuroinflammation in MPTP mice.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515493","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}

引用次数: 0

ZAKα Induces Pyroptosis of Colonic Epithelium Via the Caspase-11/GSDMD Pathway to Aggravate Colitis. ZAKα通过Caspase-11/GSDMD途径诱导结肠上皮焦亡加重结肠炎。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-24 DOI: 10.1007/s10753-025-02262-z

Song Li, Mingfei Chen, Sizhe Zheng, Waresi Abudourexiti, Feng Zhu, Zhongyuan Wang, Yanzhe Guo, Zeqian Yu, Zirui Yang, Liang Zhang, Chao Ding, Jianfeng Gong

{"title":"ZAKα Induces Pyroptosis of Colonic Epithelium Via the Caspase-11/GSDMD Pathway to Aggravate Colitis.","authors":"Song Li, Mingfei Chen, Sizhe Zheng, Waresi Abudourexiti, Feng Zhu, Zhongyuan Wang, Yanzhe Guo, Zeqian Yu, Zirui Yang, Liang Zhang, Chao Ding, Jianfeng Gong","doi":"10.1007/s10753-025-02262-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02262-z","url":null,"abstract":"ZAKα-driven ribotoxic stress response (RSR) has been shown to trigger diverse biological effects. Nevertheless, its role in the pathogenesis of ulcerative colitis (UC) remained unclear. This study aimed to determine the role of ZAKα in the development of UC. Our study found that ZAKα expression was significantly increased in colonic epithelium of UC patients and DSS-colitis mouse models. Moreover, the expression level of ZAKα mRNA showed a positive correlation with disease activity. In the colitis model, Vemurafenib, the ZAKα inhibitor, treatment reduced colonic inflammation and ameliorated intestinal mucosal barrier damage, while Anisomycin, the RSR agonist, showed the opposite effect. In vitro experiments demonstrated that Anisomycin induced pyroptosis instead of apoptosis in C26 cell line. Western blot analysis revealed that Anisomycin triggered pyroptosis via the Caspase-11/GSDMD pathway. Further animal studies confirmed that Vemurafenib downregulated this pathway, reducing colonic epithelial cell pyroptosis. Finally, blocking Caspase-11 reduced severity of DSS-induced colitis in Anisomycin-treated mice. In all, ZAKα seems to play a crucial role in the pathogenesis of colitis, as it promotes pyroptosis in colonic epithelial cells and exacerbates colitis in part by upregulating the Caspase-11/GSDMD axis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482875","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}

引用次数: 0

IRGM Inhibits the AKT/mTOR Signaling Pathway by Interacting with TRIM21 to Alleviate Sepsis-Induced Acute Lung Injury. IRGM 通过与 TRIM21 相互作用抑制 AKT/mTOR 信号通路，从而缓解败血症诱发的急性肺损伤。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-24 DOI: 10.1007/s10753-025-02265-w

Na Guo, Yu Xia, Nannan He, Lei Zhang, Jian Liu

{"title":"IRGM Inhibits the AKT/mTOR Signaling Pathway by Interacting with TRIM21 to Alleviate Sepsis-Induced Acute Lung Injury.","authors":"Na Guo, Yu Xia, Nannan He, Lei Zhang, Jian Liu","doi":"10.1007/s10753-025-02265-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02265-w","url":null,"abstract":"Acute lung injury (ALI) is a severe complication of sepsis, and its underlying pathological mechanisms remain poorly understood. This study aims to investigate the role and mechanisms by which IRGM mediates autophagy through the regulation of the AKT/mTOR signaling pathway in sepsis-induced ALI. Initially, a sepsis-induced ALI mouse model was established using cecal ligation and puncture (CLP). Our results demonstrated that Irgm1 expression was significantly upregulated in the ALI model. Subsequently, Irgm1 was knocked down in vivo using AAV vectors, and changes in ALI symptoms were assessed. In vitro, a sepsis-induced ALI cell model was generated by stimulating A549 cells with lipopolysaccharide (LPS). The effects of IRGM overexpression on autophagy and apoptosis were evaluated, and its impact on the AKT/mTOR signaling pathway was analyzed. Furthermore, mass spectrometry and co-immunoprecipitation (COIP) experiments were conducted to explore the interaction between IRGM and TRIM21. In vivo results showed that Irgm1 knockout exacerbated CLP-induced ALI, as evidenced by a significant reduction in autophagic activity, increased apoptosis, and aberrant activation of the AKT/mTOR pathway. Further cellular experiments suggested that IRGM may enhance autophagy by inhibiting the AKT/mTOR signaling pathway, thereby attenuating LPS-induced cell damage. Additionally, COIP experiments revealed that IRGM interacts with TRIM21 to inhibit AKT/mTOR pathway activation, thereby promoting autophagy and mitigating sepsis-induced ALI. In conclusion, IRGM regulates autophagy through the AKT/mTOR signaling pathway and exerts protective effects in sepsis-induced ALI, suggesting that it may serve as a potential therapeutic target for sepsis-related ALI.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491900","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}

引用次数: 0

4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway. 衣康酸4-辛酯通过Nrf2途径抑制铁下垂和促进成骨减轻绝经后骨质疏松症。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-22 DOI: 10.1007/s10753-025-02268-7

You Li, Yang Li, Pengfei Li, Lei Yang, Haijun Li

{"title":"4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway.","authors":"You Li, Yang Li, Pengfei Li, Lei Yang, Haijun Li","doi":"10.1007/s10753-025-02268-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02268-7","url":null,"abstract":"Bone marrow mesenchymal stem cells (BMSCs) play an important role in bone metabolism and tissue repair, and their ability to differentiate into osteoblasts is crucial in the treatment of bone diseases such as postmenopausal osteoporosis (PMOP). However, the function of BMSCs may be affected by ferroptosis. Ferroptosis is a cell death mode characterized by excess Fe2+ and lipid peroxidation, which significantly affects the survival rate and differentiation ability of BMSCs. This study investigated the effect of exogenous itaconate derivative 4-octyl itaconate (4-OI) on Erastin-induced BMSCs ferroptosis. The results showed that 4-OI significantly inhibited Erastin-induced BMSCs ferroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, reduced reactive oxygen species levels and oxidative damage, and restored antioxidant capacity. At the same time, 4-OI promoted the osteogenic differentiation of BMSCs. Further experiments showed that Nrf2-IN-1, an inhibitor of the Nrf2 pathway, could reverse the protective effect of 4-OI. In vivo, 4-OI was shown to reduce bone loss in ovariectomized (OVX) mice, as assessed by Micro-CT analysis. Immunofluorescence staining further revealed increased GPX4 and Nrf2 expression in vertebral tissues following 4-OI treatment. These results indicate that 4-OI improves ferroptosis of BMSCs and enhances osteogenic differentiation ability by activating the Nrf2 pathway, providing new research ideas and potential targets for the treatment of PMOP.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472479","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}

引用次数: 0

High-Resolution Untargeted Metabolomics Reveals Alternate-Day Fasting May Attenuate Diabetic Kidney Disease Progression in BTBR ob/ob Mice by Affecting the HCA, IPA and Reducing Inflammation. 高分辨率非靶向代谢组学显示隔日禁食可能通过影响HCA、IPA和减少炎症来减轻BTBR ob/ob小鼠糖尿病肾病的进展。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-21 DOI: 10.1007/s10753-025-02263-y

Huiqing Yu, Liping Yan, Jiaqing Ma, Xinduo Zhang, Hongman Wu, Yahui Yan, Hong Shen, Zhiguo Li

{"title":"High-Resolution Untargeted Metabolomics Reveals Alternate-Day Fasting May Attenuate Diabetic Kidney Disease Progression in BTBR ob/ob Mice by Affecting the HCA, IPA and Reducing Inflammation.","authors":"Huiqing Yu, Liping Yan, Jiaqing Ma, Xinduo Zhang, Hongman Wu, Yahui Yan, Hong Shen, Zhiguo Li","doi":"10.1007/s10753-025-02263-y","DOIUrl":"https://doi.org/10.1007/s10753-025-02263-y","url":null,"abstract":"Diabetic kidney disease (DKD) is one of the most severe complications of diabetes mellitus, with limited effective therapeutic interventions. Alternate-day fasting (ADF) shows potential in treating DKD, though its mechanisms are not fully understood. In this study, BTBR ob/ob mice underwent 12 weeks of ADF, and high-resolution untargeted metabolomics were performed to uncover the underlying mechanisms. After 12 weeks of ADF, the BTBR ob/ob mice exhibited weight loss, lower blood glucose and LDL-C levels, reduced 24-h urinary protein excretion, and decreased renal collagen deposition. A total of 44 metabolites were differentially expressed, with 25 up-regulated and 19 down-regulated. Notably, hyocholic acid (HCA) and indole-3-propionic acid (IPA), both products of intestinal bacteria, can modulating inflammation were differentially expressed. Furthermore, the kidneys of BTBR ob/ob mice showed significantly lower NF-κB pathway activity and reduced inflammation after 12 weeks of ADF. This study indicates that ADF may alleviate DKD progression by modulating HCA, IPA, and decreasing inflammation.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467901","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}

引用次数: 0

The Vitamin E Derivative Garcinoic Acid Suppresses NLRP3 Inflammasome Activation and Pyroptosis in Murine Macrophages. 维生素 E 衍生物甘草酸可抑制小鼠巨噬细胞中 NLRP3 炎症小体的活化和嗜热症。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-21 DOI: 10.1007/s10753-025-02269-6

Lisa Börmel, Anja R Geisler, Yvonne Hupfer, Sijia Liao, Tina Schubert, Stefan Kluge, Stefan Lorkowski, Maria Wallert

{"title":"The Vitamin E Derivative Garcinoic Acid Suppresses NLRP3 Inflammasome Activation and Pyroptosis in Murine Macrophages.","authors":"Lisa Börmel, Anja R Geisler, Yvonne Hupfer, Sijia Liao, Tina Schubert, Stefan Kluge, Stefan Lorkowski, Maria Wallert","doi":"10.1007/s10753-025-02269-6","DOIUrl":"https://doi.org/10.1007/s10753-025-02269-6","url":null,"abstract":"Excessive inflammation in cells are a common cause of inflammation-related diseases such as cardiometabolic diseases. The cellular multiprotein complex nucleotide-binding domain and leucine-rich repeat pyrin domain 3 (NLRP3) inflammasome is a cellular key modulator of inflammatory processes. In addition to classic medications, phytochemicals are known for their anti-inflammatory potential. In African folk medicine the seeds of Garcinia kola are used to support the treatment of inflammatory diseases. Of particular interest is the phytochemical garcinoic acid (GA, trans-13'-carboxy-δ-tocotrienol), which is isolated from the Garcinia kola seeds. This derivative and potential metabolite of the vitamin E congener δ-tocotrienol (T3) shows anti-inflammatory properties in vitro. However, the underlying mechanisms are largely unknown. To get better insights into the molecular mode of action, murine J774A.1 macrophages were stimulated with lipopolysaccharides (LPS) only or in combination with adenosine triphosphate (ATP), which led to canonical activation of the NLRP3 inflammasome and subsequent pyroptosis. A combined treatment with GA resulted in significantly reduced stimulation of the transcription factor nuclear factor 'ĸ-light-chain-enhancer' of activated B-cells (NF-ĸB), decreased expression of inflammasome-related genes and marked downregulation of autoproteolytic cleavage of caspase-1 (Casp-1). Consequently, GA had an inhibitory effect on pyroptosis. The results have been validated using the well-known NLRP3 inflammasome inhibitor MCC950. In conclusion, GA was shown to have relevant effects on the regulation of the NLRP3 inflammasome and pyroptosis in vitro. Our study provides new mechanistic insights into the anti-inflammatory mode of action of GA and highlights its relevance as a potential phytochemical drug for the treatment of inflammation.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467904","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}

引用次数: 0

Aberrant Subsets of Regulatory T Cells and their Correlations with Serum IL-2 in Patients with Rheumatoid Arthritis. 类风湿关节炎患者调节性T细胞亚群异常及其与血清IL-2的相关性

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-19 DOI: 10.1007/s10753-025-02248-x

Xiaoyu Zi, Huanhuan Yan, Baochen Li, Chong Gao, Xiaofeng Li, Jing Luo, Caihong Wang

{"title":"Aberrant Subsets of Regulatory T Cells and their Correlations with Serum IL-2 in Patients with Rheumatoid Arthritis.","authors":"Xiaoyu Zi, Huanhuan Yan, Baochen Li, Chong Gao, Xiaofeng Li, Jing Luo, Caihong Wang","doi":"10.1007/s10753-025-02248-x","DOIUrl":"https://doi.org/10.1007/s10753-025-02248-x","url":null,"abstract":"Aberrant number and/or dysfunction of regulatory T cells (Tregs) is associated with the development of rheumatoid arthritis (RA). This study aimed to assess the frequencies of naive Tregs (nTregs) and memory Tregs (mTregs) in the peripheral blood of RA patients and to explore their relationships with cytokine levels. This study involved 97 RA patients categorized into three groups based on Disease Activity Score 28 (DAS28) and 50 healthy controls (HCs). Flow cytometry was employed to quantify Treg subsets in peripheral blood, while serum cytokine concentrations were measured using a flow cytometry bead array. The findings revealed that three RA groups, stratified by disease activity, all exhibited a significant decrease in both the count and percentage of nTregs and an increase in the percentage of mTregs compared to HCs. Notably, the group with high RA disease activity displayed a higher percentage of mTregs than the remission group. Additionally, correlation analysis indicated that IL-2 concentrations were negatively correlated with total T, CD4 + T and Th17 cell counts, and positively correlated with the absolute count of nTregs. This study demonstrated that the count of mTregs in RA patients increased with escalating disease activity, while the count of nTregs remained unchanged. Moreover, IL-2 concentrations were positively correlated with the numbers of Tregs and nTregs, suggesting that IL-2 plays a significant role in modulating Treg subsets. Further studies on targeted therapies aligned with the distribution of mTregs and nTregs in RA patients with varying disease activity could potentially achieve effective remission.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457607","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}

引用次数: 0

Uridine Phosphorylase 1 as a Biomarker Associated with Glycolysis in Acute Lung Injury. 尿苷磷酸化酶1在急性肺损伤中与糖酵解相关的生物标志物

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-19 DOI: 10.1007/s10753-025-02270-z

Congkuan Song, Qingqing Li, Jinjin Zhang, Weidong Hu

引用次数: 0

Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome. 甲基苯丙胺和HIV-1通过激活AIM2炎性体协同诱导小胶质细胞焦亡。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-19 DOI: 10.1007/s10753-025-02266-9

Lin Miao, Haowei Wang, Xue Yang, Lisha Xu, Ruike Xu, Hanxin Teng, Yue Zhang, Yingjie Zhao, Genmeng Yang, Xiaofeng Zeng

{"title":"Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome.","authors":"Lin Miao, Haowei Wang, Xue Yang, Lisha Xu, Ruike Xu, Hanxin Teng, Yue Zhang, Yingjie Zhao, Genmeng Yang, Xiaofeng Zeng","doi":"10.1007/s10753-025-02266-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02266-9","url":null,"abstract":"Objective: Human immunodeficiency virus (HIV)-infected individuals who abuse methamphetamine (METH) exhibit more severe neurotoxicity and cognitive impairment. Pyroptosis, a programmed cell death pathway mediated by the inflammasome, has been implicated in various neurological diseases. This study aimed to elucidate the role of the AIM2 inflammasome in METH- and HIV-1 Tat-induced pyroptosis in human brain tissue and in vitro models.Methods: Postmortem brain tissue from HIV-infected individuals with a history of METH abuse was analyzed for pyroptosis markers and AIM2 inflammasome components using immunohistochemistry, immunofluorescence, and Western blotting. BV2 microglial cells were lentivirally transduced to knockdown AIM2 expression. DNA damage was assessed using Western blotting and the comet assay. Expression of pyroptosis-related proteins was evaluated by electron microscopy, Western blotting, and immunofluorescence. Cell viability was measured using the CCK8 assay.Results: Elevated levels of pyroptosis markers and AIM2 inflammasome components were observed in brain tissue from HIV-infected METH users. METH and Tat synergistically induced pyroptosis in BV2 cells in a time- and concentration-dependent manner, accompanied by DNA damage and activation of the AIM2 inflammasome. Knockdown of AIM2 significantly reduced the expression of pyroptosis-related proteins.Conclusion: METH and HIV-1 Tat proteins synergistically induce microglial pyroptosis by activating the AIM2 inflammasome through dsDNA damage. These findings suggest that targeting the AIM2 inflammasome may be a promising therapeutic strategy for HIV-associated neurocognitive disorder (HAND).","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448941","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}

引用次数: 0

Nrg4 Secreted by Brown Adipose Tissue Suppresses Ferroptosis of Sepsis-Induced Liver Injury. 褐色脂肪组织分泌Nrg4抑制脓毒症所致肝损伤铁下垂。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-17 DOI: 10.1007/s10753-024-02230-z

Linqi Feng, Jun Cui, Wenlong Chen, Lei Zhu, Panpan Li, Haitao Zhou, Yang Sun, Wei Yi

引用次数: 0