Inflammation最新文献_第9页

Colchicine Alleviates Interstitial Lung Disease in an Experimental Autoimmune Myositis Murine Model by Inhibiting the Formation of Neutrophil Extracellular Traps. 秋水仙碱通过抑制中性粒细胞外陷阱的形成缓解实验性自身免疫性肌炎小鼠模型的间质性肺病

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-17 DOI: 10.1007/s10753-024-02220-1

Feifei Li, Peipei Zhao, Liangtao Zhao, Ling Bai, Qiyan Su, Yingyue Feng, Wenlan Ma, Jiarui Zhu, Jumei Yang, Sigong Zhang

{"title":"Colchicine Alleviates Interstitial Lung Disease in an Experimental Autoimmune Myositis Murine Model by Inhibiting the Formation of Neutrophil Extracellular Traps.","authors":"Feifei Li, Peipei Zhao, Liangtao Zhao, Ling Bai, Qiyan Su, Yingyue Feng, Wenlan Ma, Jiarui Zhu, Jumei Yang, Sigong Zhang","doi":"10.1007/s10753-024-02220-1","DOIUrl":"10.1007/s10753-024-02220-1","url":null,"abstract":"Our previous study has shown that neutrophil extracellular traps (NETs) were associated with idiopathic inflammatory myopathy-related interstitial lung disease (IIM-ILD). Colchicine plays an anti-inflammatory role mainly by inhibiting the activity and chemotaxis of neutrophils. This study aims to verify therapeutic effects and mechanism of colchicine in IIM-ILD. 20 experimental autoimmune myositis (EAM) model mice were randomly divided into EAM group, colchicine groups (1, 2 mg/kg) and Cl-amidine group (positive control), five mice in the control group received sham modeling procedure. After 5 weeks, the mice were sacrificed to evaluate the degree of pulmonary interstitial lesions and the formation of NETs. Human neutrophils were pretreated with colchicine (40 nmol/L) and stimulated to form NETs. Human pulmonary microvascular endothelial cells (HPMECs) were pretreated with colchicine and stimulated with NETs, and markers of inflammation and pyroptosis were detected. Pathological staining of lung tissue showed that severity of ILD and NETs infiltration were significantly alleviated in colchicine groups (P < 0.01) and in the Cl-amidine group (P < 0.01), and the serum level of NETs was also significantly decreased in colchicine groups (P < 0.05) and in the Cl-amidine group (P < 0.05). Colchicine intervention significantly attenuated PMA-induced NETs formation in vitro (P < 0.0001). Colchicine intervention significantly reduced marker expressions of inflammasome and pyroptosis in HPMECs stimulated by NETs and in the lung tissue of EAM mice. Colchicine can alleviate ILD in EAM mice by inhibiting NETs formation, inflammasome activation and endothelial cell pyroptosis. These findings provide a basis for targeting NETs and colchicine administration in the treatment of myositis-associated ILD.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2692-2703"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835342","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

LncRNA Tug1 Regulates Post-Stroke Microglial Pyroptosis via PINK1/Parkin-Mediated Mitophagy. LncRNA Tug1通过PINK1/ parkin介导的线粒体自噬调节脑卒中后小胶质细胞焦亡。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-30 DOI: 10.1007/s10753-024-02219-8

Meiling Yao, Xiaobei Wang, Hao Lin, Hui Shu, Zongtang Xu, Ling Tang, Wenyuan Guo, Pingyi Xu

{"title":"LncRNA Tug1 Regulates Post-Stroke Microglial Pyroptosis via PINK1/Parkin-Mediated Mitophagy.","authors":"Meiling Yao, Xiaobei Wang, Hao Lin, Hui Shu, Zongtang Xu, Ling Tang, Wenyuan Guo, Pingyi Xu","doi":"10.1007/s10753-024-02219-8","DOIUrl":"10.1007/s10753-024-02219-8","url":null,"abstract":"Microglia, the central nervous system's primary immune cells, play a key role in the progression of cerebral ischemic stroke, particularly through their involvement in pyroptosis. The long non-coding RNA taurine up-regulated gene 1 (Tug1) is elevated during ischemic stroke and is critical in driving post-stroke neuroinflammation. However, the underlying molecular mechanisms remain unclear. This study explores the biological role of Tug1 and its potential mechanisms in regulating pyroptosis in microglia. We utilized an in vivo photothrombosis (PT) mice model and an in vitro oxygen-glucose deprivation and reperfusion (OGD/R) BV2 cell model to explore the mechanisms underlying ischemic stroke. Initially, we assessed the expression levels of Tug1 in the OGD/R model in vitro and the PT model in vivo. Subsequently, we investigated the impact of Tug1 on microglial pyroptosis by knocking down Tug1, silencing the PTEN-induced putative kinase 1 (Pink1) expression, and employing the mitophagy inhibitor mdivi-1. Tug1 exacerbated microglial pyroptosis by inhibiting mitophagy in both in vivo and in vitro models. The increase in mitophagy observed following Tug1 knockdown was reversed by either silencing Pink1 expression or using the mitophagy inhibitor mdivi-1. This reversal resulted in exacerbated pyroptosis and worsened neurological damage. Further mechanistic studies revealed that Tug1 knockdown significantly reduced microglial pyroptosis and alleviated neuronal damage by enhancing PINK1/Parkin-mediated mitophagy. For the first time, this study reveals that Tug1 promotes hypoxia-induced microglial pyroptosis by inhibiting PINK1/Parkin-mediated mitophagy, potentially providing a promising therapeutic target for ischemic inflammatory injury.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2677-2691"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909538","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

Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells. SARS-CoV-2刺突蛋白对人内皮细胞的持续血管炎症作用

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-31 DOI: 10.1007/s10753-024-02208-x

Mitra Gultom, Lin Lin, Camilla Blunk Brandt, Anastasia Milusev, Alain Despont, Jane Shaw, Yvonne Döring, Yonglun Luo, Robert Rieben

{"title":"Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.","authors":"Mitra Gultom, Lin Lin, Camilla Blunk Brandt, Anastasia Milusev, Alain Despont, Jane Shaw, Yvonne Döring, Yonglun Luo, Robert Rieben","doi":"10.1007/s10753-024-02208-x","DOIUrl":"10.1007/s10753-024-02208-x","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection. Here, we investigated the interaction of SARS-CoV-2 spike protein with human ECs from aortic (HAoEC) and pulmonary microvascular (HPMC) origins, cultured under physiological flow conditions. We showed that the SARS-CoV-2 spike protein triggers prolonged expression of cell adhesion markers in both ECs, similar to the effect of TNF-α. SARS-CoV-2 spike treatment also led to the release of various cytokines and chemokines observed in severe COVID-19 patients. Moreover, increased binding of leucocytes to the endothelial surface and a procoagulant state of the endothelium were observed. Transcriptomic profiles of SARS-CoV-2 spike-activated HPMC and HAoEC showed prolonged upregulation of genes and pathways associated with responses to virus, cytokine-mediated signaling, pattern recognition, as well as complement and coagulation pathways. Our findings support experimental and clinical observations of the vascular consequences of SARS-CoV-2 infection and highlight the importance of EC protection as one of the strategies to mitigate the severe effects as well as the possible post-acute complications of COVID-19 disease.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2531-2547"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909546","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}

引用次数: 0

Potential Effect of Etoricoxib in Reducing Inflammation in Methotrexate-Induced Pulmonary Injury in Rats: Role of Oxidative Stress and the TLR4/p38-MAPK/NF-κB Signaling Pathway. 依托考昔减轻甲氨蝶呤诱导的大鼠肺损伤中炎症的潜在作用：氧化应激和TLR4/p38-MAPK/NF-κB信号通路的作用

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-11-27 DOI: 10.1007/s10753-024-02198-w

Ali M Ali Abdelall, Ali Khames, Amany Abdlrehim Bekhit, Moustafa Fathy

{"title":"Potential Effect of Etoricoxib in Reducing Inflammation in Methotrexate-Induced Pulmonary Injury in Rats: Role of Oxidative Stress and the TLR4/p38-MAPK/NF-κB Signaling Pathway.","authors":"Ali M Ali Abdelall, Ali Khames, Amany Abdlrehim Bekhit, Moustafa Fathy","doi":"10.1007/s10753-024-02198-w","DOIUrl":"10.1007/s10753-024-02198-w","url":null,"abstract":"Numerous chemotherapeutic medications can have hazardous effects on the lungs, which can result in severe lung diseases. Methotrexate (MTX) is prescribed for cancer and inflammation-related disorders; nevertheless, it is exceptionally highly toxic and has multiple kinds of adverse reactions, including pulmonary injury. Our work was designed to demonstrate the ability of etoricoxib (ETO) to mitigate MTX-induced lung injury in experimental animals. Adult male Wistar rats were separated into four groups. The first group consisted of healthy controls that received carboxymethyl cellulose (1 ml/day, p.o.), the second group received a single dose of MTX (20 mg/kg/day, i.p.), the third group received ETO (10 mg/kg/day, p.o.) for three weeks, and the fourth group first received a single MTX (20 mg/kg, i.p.) and then was treated with ETO for three weeks. Concomitant treatment with ETO and MTX improved the histological structure of the lung tissue. It significantly altered the levels of oxidant/antioxidant markers, such as malondialdehyde (MDA), heme oxygenase-1 (HO-1), reduced glutathione (GSH), and nuclear factor erythroid 2-related factor 2 (Nrf-2), in favor of antioxidants. Moreover, ETO can normalize the proinflammatory cascade, which includes tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). At the molecular level, ETO downregulated the protein expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), and p38 mitogen-activated protein kinase (p38 MAPK) in inflamed rat lungs. In conclusion, our findings indicate that oral administration of ETO ameliorates MTX-induced lung injury by inhibiting oxidative stress and suppressing the TLR4/NF-κB and TLR4/p38-MAPK inflammatory signaling pathways.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2407-2416"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728186","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}

引用次数: 0

Triamcinolone Acetonide Protects Against Light-Induced Retinal Degeneration by Activating Anti-Inflammatory STAT6/Arg1 Signaling in Microglia. 曲安奈德通过激活小胶质细胞中的抗炎 STAT6/Arg1 信号来防止光诱导的视网膜退化

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-09-28 DOI: 10.1007/s10753-024-02152-w

Xiangcheng Tang, Wei Liu, Jia Liang, Xingfei Zhu, Xiangyu Ge, Dong Fang, Lirong Ling, Fanglan Yuan, Kun Zeng, Qingshan Chen, Guoming Zhang, Lili Gong, Shaochong Zhang

引用次数: 0

Interplay of α-Synuclein Oligomers and Endoplasmic Reticulum Stress in Parkinson'S Disease: Insights into Cellular Dysfunctions. 帕金森病中α-突触核蛋白寡聚体与内质网应激的相互作用：洞察细胞功能障碍。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-10-09 DOI: 10.1007/s10753-024-02156-6

Hui Zeng, Ye Liu, Xinjie Liu, Jianwei Li, Lixuan Lu, Cheng Xue, Xiao Wu, Xinran Zhang, Zijian Zheng, Guohui Lu

{"title":"Interplay of α-Synuclein Oligomers and Endoplasmic Reticulum Stress in Parkinson'S Disease: Insights into Cellular Dysfunctions.","authors":"Hui Zeng, Ye Liu, Xinjie Liu, Jianwei Li, Lixuan Lu, Cheng Xue, Xiao Wu, Xinran Zhang, Zijian Zheng, Guohui Lu","doi":"10.1007/s10753-024-02156-6","DOIUrl":"10.1007/s10753-024-02156-6","url":null,"abstract":"Oligomeric forms of α-synuclein (α-syn) are critical in the formation of α-synuclein fibrils, exhibiting neurotoxic properties that are pivotal in the pathogenesis of Parkinson's disease (PD). A salient feature of this pathology is the disruption of the protein folding capacity of the endoplasmic reticulum (ER), leading to a perturbation in the ER's protein quality control mechanisms. The accumulation of unfolded or misfolded proteins instigates ER stress. However, the onset of ER stress and the consequent activation of the Unfolded Protein Response (UPR) and Endoplasmic Reticulum-Associated Degradation (ERAD) pathways do not merely culminate in apoptosis when they fail to restore cellular homeostasis. More critically, this condition initiates a cascade of reactions involving ER-related structures and organelles, resulting in multifaceted cellular damage and, potentially, a feedback loop that precipitates neuroinflammation. In this review, we elucidate the interplay between UPR and ERAD, as well as the intricate crosstalk among the ER and other organelles such as mitochondria, lysosomes, and the Golgi apparatus, underscoring their roles in the neurodegenerative process.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1590-1606"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390323","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

Antimalarial Drug Artemotil Promotes Induction of Type 1 Regulatory T Cells. 抗疟药物阿替莫替能促进 1 型调节性 T 细胞的诱导

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-11-28 DOI: 10.1007/s10753-024-02200-5

Upasna Madan, Amit Awasthi

{"title":"Antimalarial Drug Artemotil Promotes Induction of Type 1 Regulatory T Cells.","authors":"Upasna Madan, Amit Awasthi","doi":"10.1007/s10753-024-02200-5","DOIUrl":"10.1007/s10753-024-02200-5","url":null,"abstract":"Artemisinin and its derivatives, used as front-line anti-malarial drugs, exhibit anti-inflammatory properties. They were found to suppress the generation and function of Th1 and Th17 cells while promoting the generation of Foxp3 + regulatory T cells (Tregs). However, the specific role of Artemotil (β-arteether) in modulating the generation and functions of CD4 + T cells, particularly Type 1 regulatory T cells (Tr1), remains to be explored. Tr1 cells are one of the key cell types that are essential for regulating inflammatory response through IL-10. In this study, we report that Artemotil selectively promotes generation of Tr1 cells induced by IL-27 by upregulating signature genes of Tr1 cells, such as c-Maf, AhR, prdm1, IRF-1, and Batf, while inhibiting the Th1, Th2, and Th17 cells generation. We found that co-administration of Artemotil with anti-CD3 antibody increases the induction of IL-10 and frequency of Tr1 cells while suppressing Th1 and Th17 cells in vivo. Artemotil suppresses T-cell-induced enteropathy and alleviates the signs of colitis associated with the increased frequencies of Tr1 cells. Taken together, our data suggest that Artemotil provides protection in T-cell-mediated colitis by increasing the expansion of Tr1 cells and inhibiting the generation of Th1 and Th17 cells.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2431-2443"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739262","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

Loss of Trim31 Worsens Cardiac Remodeling in a Mouse Model of Heart Failure by Enhancing the Activation of the NLRP3 Inflammasome. 在心力衰竭小鼠模型中，Trim31 的缺失会通过增强 NLRP3 炎症体的激活而加重心脏重塑。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-13 DOI: 10.1007/s10753-024-02217-w

Fengqi Duan, Huangjing Li, Bo Lu, Xiaobo Wang, Xiaojun Xu

{"title":"Loss of Trim31 Worsens Cardiac Remodeling in a Mouse Model of Heart Failure by Enhancing the Activation of the NLRP3 Inflammasome.","authors":"Fengqi Duan, Huangjing Li, Bo Lu, Xiaobo Wang, Xiaojun Xu","doi":"10.1007/s10753-024-02217-w","DOIUrl":"10.1007/s10753-024-02217-w","url":null,"abstract":"Tripartite motif-containing protein 31 (Trim31) is known to be involved in various pathological conditions, including heart diseases. Nonetheless, its specific involvement in heart failure (HF) has yet to be determined. In this study, we examined the function and mechanism of Trim31 in HF by using mice with cardiac-specific knockout (cKO) of Trim31. The HF mouse model was induced via the subcutaneous injection of isoproterenol (ISO). We observed a decrease in Trim31 expression in the heart tissues of mice with HF. Compared with wild-type (WT) mice, Trim31 cKO mice presented more severe characteristics of HF, including worsened cardiac dysfunction, hypertrophy, and fibrosis. However, these symptoms in Trim31 cKO mice were significantly reversed when they received an intramyocardial injection of recombinant adeno-associated virus (AAV) expressing Trim31. Excessive activation of the NLRP3 inflammasome, manifested by increased levels of NLRP3, ASC, cleaved Caspase-1, cleaved GSDMD, IL-1β, and IL-18, was observed in Trim31 cKO mice with HF. However, Trim31 overexpression effectively reversed the NLRP3 inflammasome activation in Trim31 cKO mice with HF. Selective inhibition of the NLRP3 inflammasome with the NLRP3 inhibitor MCC950 effectively reversed the worsened cardiac dysfunction, hypertrophy, and fibrosis observed in Trim31 cKO mice with HF. Overall, the findings from this study reveal a crucial role of Trim31 in HF. Trim31 deficiency may contribute to the progression of HF by promoting cardiac hypertrophy, fibrosis, and inflammation by facilitating the activation of the NLRP3 inflammasome. Therefore, Trim31 may hold significant potential as a therapeutic target for the treatment of HF.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2650-2662"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822036","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

GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling. GZMK 通过与 CCL5 相互作用并激活 ERK 信号，促进实验性类风湿性关节炎的进展。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-11-04 DOI: 10.1007/s10753-024-02166-4

Liting Xu, Hui Wang, Congcong Sun, Qingyu Zhao, Lili Wang, Qianqian Yan, Jialin Wang, Na Lin, Chunfang Liu

{"title":"GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling.","authors":"Liting Xu, Hui Wang, Congcong Sun, Qingyu Zhao, Lili Wang, Qianqian Yan, Jialin Wang, Na Lin, Chunfang Liu","doi":"10.1007/s10753-024-02166-4","DOIUrl":"10.1007/s10753-024-02166-4","url":null,"abstract":"Synovial over-proliferation is a key event in the progression of rheumatoid arthritis (RA) disease. Ferroptosis may be essential for maintaining the balance between synovial proliferation and death. This study aimed to investigate the molecular mechanisms mediating the activation and ferroptosis of collagen-induced arthritis (CIA)-synovial fibroblasts (SFs). Differentially expressed genes (DEGs) in the synovial tissues of CIA rats and normal rats were screened through sequencing. The GSE115662 dataset from the GEO database was analyzed and screened for DEGs. The viability, proliferation, migration, invasion, cell cycle, and apoptosis of CIA-SFs were analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell migration, and invasion assays. The ferroptosis of CIA-SFs was assessed using matching reagent kits to detect indicators like reactive oxygen species, ferrous iron, malondialdehyde, glutathione, and superoxide dismutase. The interaction between Granzyme K (GZMK) and C-C motif chemokine 5 (CCL5) was determined by coimmunoprecipitation assay. We found abnormal GZMK expression in the GSE115662 database and mRNA sequencing data. GZMK was overexpressed in CIA-SFs, and GZMK promoted cell proliferation, migration, invasion, inflammation, and decreased cell apoptosis and ferroptosis in CIA-SFs. GZMK could interact with CCL5 to activate the ERK signaling. GZMK and CCL5 knockdown improved by reducing arthritis scores, redness and swelling of paws, and pathological changes in joint synovium of CIA rats. CCL5 overexpression reversed the effects of GZMK silencing on CIA-SFs cell proliferation, migration, invasion, apoptosis, and ferroptosis. We confirmed that GZMK accelerated experimental rheumatoid arthritis progression by interacting with CCL5 and activating the ERK signaling.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1940-1956"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568272","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

Cell Division Cycle 42 Improves Renal Functions, Fibrosis, Th1/Th17 Infiltration and Inflammation to Some Degree in Diabetic Nephropathy. 细胞分裂周期 42 可在一定程度上改善糖尿病肾病患者的肾功能、纤维化、Th1/Th17 浸润和炎症。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-11-13 DOI: 10.1007/s10753-024-02169-1

Na Zhao, Chuwen Feng, Yuehui Zhang, Huijun Chen, Jian Ma

{"title":"Cell Division Cycle 42 Improves Renal Functions, Fibrosis, Th1/Th17 Infiltration and Inflammation to Some Degree in Diabetic Nephropathy.","authors":"Na Zhao, Chuwen Feng, Yuehui Zhang, Huijun Chen, Jian Ma","doi":"10.1007/s10753-024-02169-1","DOIUrl":"10.1007/s10753-024-02169-1","url":null,"abstract":"Our two previous studies observed that cell division cycle 42 (CDC42) was lower and correlated with improved renal function and inflammation in diabetic nephropathy (DN) patients, and CDC42 inhibited renal tubular epithelial cell fibrosis and inflammation under high glucose condition. Sequentially, this current study aimed to investigate the effect of CDC42 on improving renal function, fibrosis, and inflammation in DN mice, and its interaction with T cell receptor (TCR) related pathways. Mice were treated by streptozotocin to construct early-stage DN model, then transfected with CDC42 overexpression adenovirus, followed by simultaneous treatment of LY294002 (PI3K/AKT inhibitor) and CI-1040 (ERK inhibitor), respectively. CDC42 reduced blood glucose, creatinine, and 24 h urine protein in DN mice, but only showed a tendency to decrease blood urea nitrogen without statistical significance. Hematoxylin&eosin staining revealed that CDC42 descended the glomerular volume, basement membrane thickness, and inflammatory cell infiltration in kidney. Meanwhile, CDC42 lowered fibronectin, TGF-β1, and Collagen I expressions in kidney, but not decreased α-SMA significantly. Besides, CDC42 decreased T-helper (Th) 1 and Th17 cells in kidney, and reduced serum IFN-γ, IL-1β, IL-17A, and TNF-α but not IL-6. Regarding TCR-related pathways, CDC42 activated AKT and ERK pathways but not JNK pathway. However, the treatment of LY294002 and CI-1040 had limited effect on attenuating CDC42's functions on renal function and fibrotic markers. CDC42 improves renal functions, fibrosis, Th1/Th17 infiltration and inflammation to some degree in DN mice, these functions may be independent to AKT and ERK pathways.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1987-1997"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619373","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