Inflammation最新文献

{"title":"Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis.","authors":"Lin Chen, Zhihao Wang, Yuyan Zhang, Qingtian Zhu, Guotao Lu, Xiaowu Dong, Jiajia Pan, Keyan Wu, Weijuan Gong, Weiming Xiao, Yanbing Ding, Yanyan Zhang, Yaodong Wang","doi":"10.1007/s10753-024-02173-5","DOIUrl":"10.1007/s10753-024-02173-5","url":null,"abstract":"<p><p>Damage to pancreatic acinar cells (PAC) and intracellular metabolic disturbances play crucial roles in pancreatic necrosis during acute pancreatitis (AP). Phosphoglycerate kinase 1 (PGK1) is a crucial catalytic enzyme in glycolysis. However, the impact of PGK1-involving glycolysis in regulating metabolic necrosis in AP is unclear. Transcriptome analysis of pancreatic tissues revealed significant changes in the glycolysis pathway and PGK1 which positively correlated with the inflammatory response and oxidative stress injury in AP mice. Furthermore, we observed a substantial increase in PGK1 expression in damaged PAC, positively correlating with PAC necrosis. Treatment with NG52, a specific PGK1 inhibitor, ameliorated pancreatic necrosis, inflammatory damage, and oxidative stress. Transcriptomic data before and after NG52 treatment along with the Programmed Cell Death database confirmed that NG52 protected against PAC damage by rescuing impaired autophagy in AP. Additionally, the protective effect of NG52 was validated following pancreatic duct ligation. These findings underscore the involvement of PGK1 in AP pathogenesis, highlighting that PGK1 inhibition can mitigate AP-induced pancreatic necrosis, attenuate inflammatory and oxidative stress injury, and rescue impaired autophagy. Thus, the study findings suggest a promising interventional target for pancreatic necrosis, offering novel strategies for therapeutic approaches to clinical AP.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2036-2050"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545279","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":"\"The Ameliorative Effect of Interleukin-17A Neutralization on Doxorubicin-Induced Cardiotoxicity by Modulating the NF-κB/NLRP3/Caspase-1/IL-1β Signaling Pathway in Rats\".","authors":"Mostafa D Hassen, Nahla O Mousa, Sara M Radwan, Refaat M Gabre","doi":"10.1007/s10753-024-02187-z","DOIUrl":"10.1007/s10753-024-02187-z","url":null,"abstract":"<p><p>Doxorubicin (DOX) is used as a chemotherapeutic drug for treating cancer. Nevertheless, it causes damage to the heart by activating inflammatory pathways, resulting in cardiotoxicity. Imbalance in cytokine production is a crucial component that might trigger the initiation of inflammatory processes. Inflammatory cytokines could be targeted therapies against cardiovascular diseases (CVDs). Interleukin-17A (IL-17A) is a cytokine that promotes inflammation and stimulates harmful immunological reactions. The objective of the study was to determine the efficacy of secukinumab (SEC), a completely human monoclonal IgG1/κ antibody that targets IL-17A, in ameliorating DOX-induced cardiotoxicity (DIC). We administered 2.5 mg/kg of DOX intraperitoneally to male Wistar rats three times a week for 2 weeks and simultaneously administered 0.9 mg/kg of SEC along with 2.5 mg/kg of DOX injection three times a week for a duration of two weeks. The findings indicated that DOX induced damage to the heart tissue, resulting in a significant rise in indicators of cardiotoxicity (P < 0.001), as well as oxidative stress and inflammation. DIC may have arisen from DOX's activation of the Pyrin domain containing 3 (NLRP3) inflammasome and the nuclear factor kappa beta (NF-κB) pathway. The co-administration of SEC successfully reversed all DOX-induced abnormalities by restoring cardiac functions to their baseline levels, decreasing levels of inflammatory mediators such as IL-17A and interleukin-1β (IL-1β), and improving oxidative stress by reducing levels of malondialdehyde (MDA) and increasing levels of reduced glutathione (GSH). Furthermore, it mitigated the heightened activation of the NF-κB/NLRP3 pathway caused by DOX. This study shows that IL-17A neutralization can prevent DIC by regulating the NF-κB/NLRP3/Caspase-1/IL-1β pathway to be used as potential therapeutic target for CVDs.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2244-2257"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597008","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":"p62 Binding to Protein Kinase C Regulates HIV-1 gp120 V3 Loop Induced Microglial Inflammation.","authors":"Huili Wang, Qin Zuo, Xinyi Li, Yuanyuan Liu, Limeng Gan, Linlin Wang, Yin Rao, Rui Pan, Jun Dong","doi":"10.1007/s10753-024-02229-6","DOIUrl":"10.1007/s10753-024-02229-6","url":null,"abstract":"<p><p>The main pathogenic mechanism of HIV-associated neurocognitive disorders (HAND) is neuronal apoptosis induced by inflammatory mediators, in which microglial inflammation plays a crucial role. However, the exact pathogenic mechanism remains unclear. Previous studies have shown that the HIV-1 gp120 V3 loop can trigger inflammation in CHME-5 microglia. p62 is a post-translational modified multidomain protein that is involved in the regulation of autophagy and is closely related to neuroinflammation. In this study, we found that p62 knockout down-regulated the expression of MCP-1, IL-6 and COX-2, and improved the inflammation of HIV-1 gp120 V3 loop induced microglia, while overexpression of p62 up-regulated the expression of MCP-1, IL-6 and COX-2, and promoted the inflammation of microglia. In addition, protein kinase C (PKC) knockout down-regulated the expression of MCP-1, IL-6 and COX-2 and inhibited the activation of IKK/ NF-κ B pathway, while tumor necrosis factor receptor-associated factor 6 (TRAF6) knockout had no significant effect on the expression of MCP-1, IL-6 and COX-2. Co-immunoprecipitation showed that p62 was bound and interacted with PKC. Inhibition of IKK/ NF-κ B pathway can down-regulate the expression of MCP-1, IL-6 and COX-2, and improve the inflammatory response of microglia. Our research further found that inhibition of IKK/ NF-κ B can decrease the expression of Caspase-3 and reduce the apoptosis of neurons in the co-culture of CHME-5 microglia and primary mouse neurons. The results of this study suggest that HIV-1 gp120 V3 loop induced CHME-5 microglial inflammation may be activated by the direct binding of p62 and PKC through the IKK/ NF-κ B signaling pathway, and these findings provide an important reference for the prevention and treatment of HAND.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2772-2782"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894103","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":"RNA-seq Based Transcriptome Analysis Reveals Role of Myoglobin in Rheumatoid Arthritis.","authors":"Haibin Wang, Xin Tian, Le Ji, Liang Shi, Ying Wang","doi":"10.1007/s10753-024-02151-x","DOIUrl":"10.1007/s10753-024-02151-x","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which manifests as joint destruction and bone erosion, could be caused by both genetic and environmental factors. Currently, the causes of RA are unknown, and targeted therapies are often associated with side effects and contraindications. The detection rate of RA in women is higher than men (3:1), however, there is still a lack of comprehensive understanding of the relationship between sex and RA. We hypothesized gender differences in RA prevalence and their associated mechanisms by performing genome-wide transcriptome analysis of synovial biopsy samples. The results indicated that myoglobin (MB) was differentially expressed between males and females, with higher expression in males than females in healthy populations, while the opposite was observed in RA patients. MB interacted with HLA class II histocompatibility antigen, DM beta (HLA-DMB) and the inflammatory factor interleukin 6 (IL-6) in the human synovial cell line MH7A.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1745-1759"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390324","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":"Brief Disruption of Circadian Rhythms Alters Intestinal Barrier Integrity and Modulates DSS-Induced Colitis Severity in Mice.","authors":"Bibiana E Barrios, Cristian E Jaime, Angela A Sena, Marina de Paula-Silva, Cristiane D Gil, Sonia M Oliani, Silvia G Correa","doi":"10.1007/s10753-024-02162-8","DOIUrl":"10.1007/s10753-024-02162-8","url":null,"abstract":"<p><p>Physiological processes in organisms exhibit circadian rhythms that optimize fitness and anticipate environmental changes. Luminal signals such as food or metabolites synchronize bowel activity, and disruptions in these rhythms are linked to metabolic disorders and gastrointestinal inflammation. To characterize the intrinsic intestinal rhythms and assess disruptions due to continuous darkness or light exposure, C57BL/6 mice were exposed to standard light-dark conditions or continuous light/darkness for 48 h, with evaluations at four timepoints. We assessed intestinal morphology, mucus production, nitric oxide levels and permeability. Under standard light: dark cycles, mice showed changes in intestinal morphology consistent with normal tract physiology. Continuous light exposure caused marked alterations in the small intestine´s epithelium and lamina propria, reduced nitric oxide production in the colon, and predominant neutral mucins. Enhanced permeability was indicated by higher FITC-dextran uptake and increased frequency of IgG-coated bacteria. Additionally, the 48 h-disruption influenced DSS-induced colitis with attenuation in L:L group, or exacerbation in D:D group, of clinical signs. These findings highlight the critical role of circadian rhythms in gut histoarchitecture and function, demonstrating that short-term disruptions in light-dark cycles can compromise intestinal barrier integrity and impact inflammatory outcomes.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1900-1911"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464274","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":"Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.","authors":"Jyh-Hong Lee, Yao-Hsu Yang, Yu-Tsan Lin, Li-Chieh Wang, Hsin-Hui Yu, Ya-Chiao Hu, Bor-Luen Chiang","doi":"10.1007/s10753-024-02159-3","DOIUrl":"10.1007/s10753-024-02159-3","url":null,"abstract":"<p><p>Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5 IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1 IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1839-1862"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521833","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-17A-Induced Redox Imbalance and Inflammatory Responses in Mice Lung via Act1-TRAF6-IKBα Signaling Pathway: Implications for Lung Disease Pathogenesis.","authors":"Ekta Swarnamayee Panda, Avtar Singh Gautam, Shivam Kumar Pandey, Rakesh Kumar Singh","doi":"10.1007/s10753-024-02199-9","DOIUrl":"10.1007/s10753-024-02199-9","url":null,"abstract":"<p><p>IL-17A is a potent proinflammatory cytokine that plays a crucial role in the pathogenesis of various lung diseases. This study focused on the evaluation of the role of IL-17 receptor signaling through one-week intranasal exposure of IL-17A in lung tissues of BALB/c mice. IL-17A triggered inflammatory responses in the mice lungs and led to changes in the morphological alveolar arrangements. Exposure of IL-17A induced redox imbalance by triggering an increase in the level of the pro-oxidants (reactive oxygen species, nitrite and malondialdehyde) and reduction of the levels of antioxidant proteins (glutathione, superoxide dismutase and catalase) in the lung tissue. IL-17A also caused a significant elevation in the levels of proinflammatory cytokines lines including TNF-α, IL-1β and IL-6, in lung tissue as well as in plasma. More interestingly, these changes were accompanied by the alterations in IL-17 receptor downstream signaling through activation of IL-17R-Act1-TRAF6-IKBα-mediated pathway. IL-17A exposure also caused lung tissue injury, recruitment and polarization of immune cells from anti-inflammatory to pro-inflammatory. This study clearly demonstrated the role of IL-17A-induced signaling in worsening lung inflammatory diseases, and hence points towards its emergence as an important therapeutic target to control lung inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2417-2430"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739264","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":"Fibroblast Growth Factor 21 Confers Protection Against Asthma Through Inhibition of NLRP3 Inflammasome Activation.","authors":"Yudong Liu, Jingxian Li, Zhenyu Wu, Shiyu Wu, Xinwei Yang","doi":"10.1007/s10753-024-02222-z","DOIUrl":"10.1007/s10753-024-02222-z","url":null,"abstract":"<p><p>Fibroblast growth factor 21 (FGF21) modulates the inflammatory response in a range of pathological conditions. However, whether FGF21 modulates asthma remains unexplored. This study sought to investigate its function in asthma using an ovalbumin (OVA)-induced mouse model. Levels of FGF21 were observed to be elevated in mice exhibiting asthmatic symptoms. FGF21 knockout (KO) mice exhibited exacerbated asthmatic pathologies, marked by heightened infiltration of inflammatory cells and elevated release of inflammatory cytokine, compared to wild-type (WT) mice with OVA challenge. Adeno-associated virus (AAV)-mediated overexpression of FGF21 significantly reversed asthmatic pathologies in both WT and FGF21 KO mice. Activated NLRP3 inflammasome was observed in WT mice following OVA challenge, and this response was intensified in FGF21 KO mice, manifested by an upregulation of NLRP3, ASC, cleaved Caspase-1, cleaved Gasdermin D (GSDMD), IL-1β, and IL-18. Pharmacological suppression of NLRP3 ameliorated the aggravated asthmatic pathologies observed in FGF21 KO mice after OVA challenge. Overall, the present work underscores the pivotal function of FGF21 in the pathogenesis of asthma and suggests that FGF21 could serve as a potential target for therapeutic interventions.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2720-2731"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894093","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":"Inhibition of Mitochondrial Succinate Dehydrogenase with Dimethyl Malonate Promotes M2 Macrophage Polarization by Enhancing STAT6 Activation.","authors":"Chaowen He, Pengfei Chen, Luwen Ning, Xiuping Huang, Huimin Sun, Yuanyuan Wang, Yanli Zhao, Changchun Zeng, Dongsheng Huang, Hanchao Gao, Mengtao Cao","doi":"10.1007/s10753-024-02207-y","DOIUrl":"10.1007/s10753-024-02207-y","url":null,"abstract":"<p><p>Macrophages exhibit diverse phenotypes depending on environment status, which contribute to physiological and pathological processes of immunological diseases, including sepsis, asthma, multiple sclerosis and colitis. The alternative activation of macrophages is tightly regulated to avoid excessive activation and damage of tissues and organs. Certain works characterized that succinate dehydrogenase (SDH) altered function of macrophages and promoted inflammatory response in M1 macrophages via mitochondrial reactive oxygen species (ROS). However, the effect of succinate dehydrogenase on M2 macrophage polarization remains incompletely understood. We employed dimethyl malonate (DMM) to inhibit succinate dehydrogenase activity and took use of RNA-seq to analyze the changes of inflammatory response of LPS-activated M1 macrophages or IL 4-activated M2 macrophages. Our data revealed that inhibition of SDH with DMM increased expression of M2 macrophages-associated signature genes, including Arg1, Ym1 and Mrc1. Consistent with previous work, we also observed that inhibition of SDH decreased the expression of IL-1β and enhanced the levels of IL-10 in M1 macrophages. Additionally, inhibition of SDH with DMM inhibited the production of chemokines, such as Cxcl3, Cxcl12, Ccl20 and Ccl9. DMM also amplified the M2 macrophages-related signature genes in IL-13-activated M2 macrophages. Mechanistic studies revealed that DMM promoted M2 macrophages polarization through mitochondrial ROS dependent STAT6 activation. Blocking ROS with mitoTEMPO or inhibiting STAT6 activation with ruxolitinib abrogated the promotion effect of DMM on M2 macrophages. Finally, dimethyl malonate treatment promoted peritoneal M2 macrophages differentiation and exacerbated OVA-induced allergy asthma in vivo. Collectively, we identified SDH as a braker to suppress M2 macrophage polarization via mitochondrial ROS, suggesting a novel strategy to treatment of M2 macrophages-mediated inflammatory diseases.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2516-2530"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978268","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":"The Role of CCL11-CCR3 Induced Mitochondrial Dysfunction and Oxidative Stress in Cognitive Impairment in Early-onset Schizophrenia: Insights from Preclinical Studies.","authors":"Xing Luo, Jiangwen Dong, Tao Li","doi":"10.1007/s10753-025-02344-y","DOIUrl":"https://doi.org/10.1007/s10753-025-02344-y","url":null,"abstract":"<p><p>Abnormal cytokine expression has been implicated as a potential contributor to neurodegeneration. This study aimed to investigate the plasma cytokine profiles in patients with early-onset schizophrenia (SCZ) and to explore the molecular mechanisms underlying the role of the key cytokine CCL11 in contributing to cognitive impairment. Plasma concentrations of 44 cytokines were quantified in individuals with SCZ. The effects of CCL11 on mitochondrial function were examined in vitro using primary hippocampal neurons. An in vivo model was subsequently developed by administering CCL11 into the lateral ventricle. The impact of the CCL11-CCR3 signaling pathway on mitochondrial function, oxidative stress, and cognitive function within the hippocampus was assessed using a combination of behavioral testing, molecular biology experiments, transcriptomic analysis, and non-targeted metabolomics. In individuals with SCZ, CCL11 and IL-13 levels were notably higher than in controls. In vitro, CCL11 exposure caused mitochondrial dysfunction and increased reactive oxygen species in hippocampal neurons. In vivo, CCL11-treated mice showed cognitive deficits, mitochondrial fission, and neuroinflammation in the hippocampus. Comprehensive integration of transcriptomic and metabolomic data revealed that CCL11 significantly disrupted the Glucokinase/Glucose-6-phosphate metabolism pathway, coinciding with elevated metabolites indicative of oxidative damage. Finally, downregulation of the CCR3 receptor in the hippocampus mitigated CCL11-induced oxidative stress, mitochondrial dysfunction, and cognitive impairment. CCL11 causes cytotoxicity in neurons by increasing oxidative stress and mitochondrial dysfunction. In a mouse model, knockout of the CCR3 receptor alleviates CCL11-induced cognitive impairment, mitochondrial dysfunction, and oxidative stress.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730102","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}