Inflammation最新文献

{"title":"Targeting SLC7 A11 Ameliorates Ulcerative Colitis by Promoting Efferocytosis Through the ERK1/2 Pathway.","authors":"Meiyi You, Jichang Li, Xin Wang, Yucun Liu, Shanwen Chen, Pengyuan Wang","doi":"10.1007/s10753-025-02312-6","DOIUrl":"https://doi.org/10.1007/s10753-025-02312-6","url":null,"abstract":"<p><strong>Objective and design: </strong>This study investigates the effect and underlying mechanism of targeting SLC7A11 in mitigating dextran sulfate sodium (DSS)-induced intestinal inflammation and injury in colitis.</p><p><strong>Methods: </strong>We utilized wild-type and SLC7A11^-/+ mice to assess the inflammatory damage in DSS-induced colitis in vivo. In vitro, colon tissues from patients with ulcerative colitis were analyzed to compare SLC7A11 expression between inflamed and non-inflamed regions. Further mechanistic insights were obtained using Caco-2 cells and bone marrow-derived dendritic cells (BMDCs).</p><p><strong>Results: </strong>In human colon tissues, SLC7A11 expression was significantly elevated in inflamed regions compared to non-inflamed areas, particularly in dendritic cells. In vivo inhibition of SLC7A11 markedly alleviated DSS-induced colitis symptoms. In vitro, suppressing SLC7A11 restored the integrity of the Caco-2 monolayer intestinal epithelial model. Both knockout and inhibition of SLC7A11 enhanced ERK1/2 phosphorylation and increased efferocytosis in BMDCs.</p><p><strong>Conclusions: </strong>Targeting SLC7A11 augments dendritic cell efferocytosis and preserves intestinal epithelial barrier function, potentially offering a therapeutic avenue for alleviating ulcerative colitis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012854","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":"Single-Cell RNA Sequencing Reveals the Immune Landscape of Granulomatous Mastitis.","authors":"Yao Zhou, Xianguang Deng, Hui Ruan, Xing Xue, Zixuan Hu, Jie Gong, Shiting Wu, Lifang Liu","doi":"10.1007/s10753-025-02310-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02310-8","url":null,"abstract":"<p><p>Granulomatous mastitis (GM) is a form of non-lactational breast inflammation that is closely associated with autoimmune processes, however its underlying pathogenesis remains elusive. In this study, we employed single-cell RNA sequencing (scRNA-seq) to conduct a comparative analysis of GM lesion tissues versus normal breast tissues, thereby unveiling the immune profile of GM tissues. Our investigation centered on T and NK cells, macrophages, epithelial cells, and endothelial cells. Notably, we observed a substantial infiltration of immune cells in GM tissues, accompanied by immune disorders, an elevation in Th1 cell counts, enrichment of the toll-like receptor (TLR) pathway, and upregulation of various factors including interferon-γ (IFN-γ), C-C motif chemokine ligand 3 (CCL3), CCL4, chemokine (C-X-C motif) ligand (CXCL) 13, CD69, signal transducer and activator of transcription 1 (STAT1), and heat shock protein family A member 1A (HSPA1A). Furthermore, the macrophage subpopulations in GM tissues exhibited a transition to a pro-inflammatory phenotype, enriched for pathways such as interferon-γ (IFN-γ), IFN-α, interleukin-6/janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3), and tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB). Mammary luminal cells demonstrated an impaired estrogenic profile yet displayed upregulation of prolactin downstream signaling pathways, namely the JAK/STAT and mitogen-activated protein kinase (MAPK) pathways. Additionally, vascular endothelial cells were found to recruit immune cells and exhibited a prominent angiogenic profile in GM tissues. Cellular interaction analysis unveiled an intricate network of interactions between mesenchymal and immune cells. This study provides a comprehensive immune landscape of granulomatous mastitis and offers some potential therapeutic targets for the disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998462","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":"TIPE2 Alleviates Sepsis-induced Lung Injury By Inhibiting PANoptosis in Murine Alveolar Macrophages.","authors":"Yuxuan Wang, Min Yuan, Jingxue Qin, Xue Chen, Zihan Lei, Qian Kong, Qian Wang, Xuemin Song, Xiaojing Wu","doi":"10.1007/s10753-025-02288-3","DOIUrl":"https://doi.org/10.1007/s10753-025-02288-3","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) is a life-threatening condition with high mortality rates, and its underlying mechanisms remain poorly understood. This study investigates the role of TNF-α-induced protein 8-like 2 (TIPE2) in modulating PANoptosis, an integrated form of programmed cell death that includes apoptosis, necroptosis, and pyroptosis, in the context of sepsis-induced lung injury. We utilized a cecal ligation and puncture (CLP) mouse model to examine the effects of TIPE2 knockout and overexpression on lung injury, inflammation, and cell death pathways. Our findings demonstrate that TIPE2 knockout exacerbates lung injury by promoting the abnormal activation of PANoptosis-related proteins, leading to increased inflammation and tissue damage. In contrast, overexpression of TIPE2 in macrophages significantly reduces these effects by inhibiting the ZBP1-dependent PANoptosis pathway via TRIF signaling. These results highlight the crucial role of TIPE2 in maintaining the balance between cell survival and death during sepsis and suggest that targeting TIPE2 could be a novel therapeutic strategy for treating sepsis-related lung injury.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008481","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":"Acute and Long-Term Consequences of Neonatal NMDA Blockade in the Cx3cr1 Knock-Out Mouse.","authors":"Felipe A Méndez, Mayra Itzel Torres-Flores, Benito Ordaz, Fernando Peña-Ortega","doi":"10.1007/s10753-025-02272-x","DOIUrl":"https://doi.org/10.1007/s10753-025-02272-x","url":null,"abstract":"<p><p>Neuron-microglia communication through the fractalkine pathway is a critical factor mediating microglial proliferation, migration, release of mediators, and clearance of cellular debris, as well as the function of neuronal NMDA receptors. Disruption of the fractalkine-mediated microglia-neuron communication is associated with divergent outcomes, from damaging to protective, in different neurological conditions (including schizophrenia and epilepsy). In the present work we explore the impact of the absence of the fractalkine receptor (CX3CR1) after neonatal blockade of NMDA receptors, which induces acute and long-term alterations in behavior, neuronal integrity and excitability. Wild-type (WT) and Cx3cr1^-/- (KO) mice of both sexes randomly received either a low (0.5 mg/kg) or high dose (1 mg/kg) of MK-801 (NMDA receptor antagonist) or saline, for five consecutive days, during early postnatal development. Neuronal apoptosis was assessed at a midpoint of the pharmacological protocol. Survival and growth rates were determined up to adulthood when innate behaviors, unconditioned anxiety, contextual memory and seizure susceptibility were evaluated, as well as hippocampal local field potential and sensory gating. CX3CR1 depletion and neonatal MK-801 treatment had a synergistic acute effect, increasing neuronal apoptosis and overall mortality. Both factors independently induced long-lasting impairments in the wide array of behavioral tasks assessed during adulthood. However, low MK-801 dose treatment greatly augmented the mortality of pentylenetetrazol-induced seizures in WT mice, an effect prevented by CX3CR1 depletion. MK-801 treatment induced a shift in the power spectrum of the hippocampal local field potential towards higher frequencies that was averted in Cx3cr1^-/- mice by an opposite shift. Our results reveal that CX3CR1 depletion severely increases the vulnerability to neonatal NMDA antagonism with additional complex interactions regarding cognitive and neurophysiological effects, which should be considered in the context of neuron-microglia miscommunication in many neurological disorders including schizophrenia and epilepsy.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995640","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":"A Quinoxaline Derivative as a New Therapeutic Agent for Sepsis through Suppression of TLR4 Signaling Pathways.","authors":"Hamza Hanieh, Manal A Alfwuaires","doi":"10.1007/s10753-025-02292-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02292-7","url":null,"abstract":"<p><p>Sepsis is a severe systemic inflammatory syndrome and one of the leading causes of global morbidity and mortality. Preclinical studies have identified several quinoxaline-based compounds with anti-inflammatory properties, but their effects in sepsis have not been investigated. This study aimed to identify a quinoxaline derivative with anti-inflammatory properties in sepsis. Examining the inflammatory response of primary mouse macrophages to Lipopolysaccharides (LPS) revealed that 2-methoxy-N-(3-quinoxalin-2-ylphenyl)benzamide (2-MQB) is a promising molecule. It suppressed the production of several inflammatory cytokines, including Interleukin-1β (IL-1β), IL-6, IL-12p70, Interferon-γ (IFN-γ), IFN-β, and Tumor necrosis factor-α (TNF-α). Importantly, 2-MQB inhibited the transcriptional activities of Toll-like receptor 4 (TLR4) signaling pathways, including Nuclear factor-κB (NF-κB) and Interferon regulatory factor 3 (IRF3). This was accompanied by lower expression of TLR4, Myeloid differentiation primary response 88 (MyD88), TIR Domain-containing adaptor molecule 1 (Trif), and TNF Receptor-associated factor 3 (Traf3). Additionally, 2-MQB selectively reduced the expression of genes encoding CD80, CD86, and Programmed death-ligand 1 (PD-L1). In vivo, 2-MQB improved mice survival, mitigated tissue damage in the spleen, kidney, and lung, and reduced pro-inflammatory cytokine levels in both LPS-induced endotoxin shock and Cecal ligation and puncture (CLP) models. Notably, 2-MQB decreased the numbers of CD4⁺ and CD8⁺ T cells in the spleen and inhibited TLR4 signaling pathways in LPS-induced endotoxemia. In conclusion, these results introduce the quinoxaline derivative 2-MQB as a potential therapeutic agent for sepsis by inhibiting TLR4 signaling pathways, paving the way for future clinical applications.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006867","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":"Integrated Analysis of Single-Cell and Transcriptome Data Reveals the Role and Regulatory Mechanisms of Neuroinflammation in Parkinson's Disease.","authors":"Yao Geng, Rui-Yu Wang, Man-Yu Dong, Yi-Lun Qian, Xi-Hui Wang, Wen-Wen Xia, Ying Shen, Ke-Zhong Zhang","doi":"10.1007/s10753-025-02306-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02306-4","url":null,"abstract":"<p><p>There is increasing interest in developing therapeutic interventions aimed at preventing neuroinflammation in Parkinson's disease (PD). However, the specific characteristics of inflammation across different cell types and the underlying mechanisms of PD-related inflammation remain inadequately understood. In this study, we conducted an analysis of single-cell RNA sequencing (scRNA-seq) and microarray data derived from human PD midbrain tissue, specifically focusing on the substantia nigra compacta (SNc). These datasets were sourced from the (GEO) database. We utilized GSVA, GSEA, as well as KEGG and GO analyses to explore transcriptional variations associated with PD. Furthermore, trajectory and SCENIC analyses were conducted to uncover the mechanisms underlying PD progression. Subsequent animal and cellular experiments validated the role of the regulon in regulating neuroinflammation. Results: Our analysis revealed that microglia displayed the highest levels of inflammatory activity, characterized by an increased abundance of microglia in the proinflammatory activated state within the midbrain and SNc of PD patients. This finding was further validated in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The transcription factor STAT3 demonstrated significant upregulation and was implicated in promoting the inflammatory response and activating microglia within the PD context. In the 1-methyl-4-phenylpyridine (MPP +)-induced BV2 cell model, inhibition of STAT3 led to reduced levels of inflammation, hindered STAT3 phosphorylation, and decreased the production of inflammatory factors. Furthermore, the downregulation of P-STAT3 alleviated the harmful effects on SH-SY5Y cells that were cocultured in the conditioned medium. Conclusions: Our study underscored the pivotal role of the transcription factor STAT3 as a central regulator of proinflammatory activation in microglia within PD. These findings offer fresh insights into PD pathogenesis and suggest potential avenues for the development of novel therapeutic strategies.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985040","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 Macrophage Activation by Minocycline Attenuates CCI-Induced Neuropathic Pain.","authors":"Yan-Zhe Ji, Zhi-Hao Lin, Cai-Xian Liao, Qian Wang, Fang-Yu Chen, Wen-Feng Su, Ya-Yu Zhao, Gang Chen, Zhong-Ya Wei","doi":"10.1007/s10753-025-02300-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02300-w","url":null,"abstract":"<p><p>Neuropathic pain is characterized by a high prevalence and associated with a variety of disorders of the peripheral and central nervous systems. It remains a major challenge for clinical management due to lack effective treatments. Our previous studies have demonstrated that nerve injury-induced neuroinflammation plays a critical role in regulating the development and maintenance of neuropathic pain. In the present study, we found that chronic constriction injury (CCI) led to a significant increase in the number of macrophages at the site of injured nerves. To elucidate the role of macrophage activation in CCI-induced neuropathic pain, we employed chemical agents, including clodronate liposomes, which is known for their ability to deplete macrophages, and minocycline, an inhibitor of macrophage function. Both intravenous injection of liposome-encapsulated clodronate and intrasciatic delivery of minocycline effectively attenuated CCI-induced mechanical and heat hyperalgesia. Furthermore, transfer of polarized M2 macrophages significantly alleviated CCI-induced neuropathic pain, but not under the condition of M1 macrophage transfer. Mechanistically, our findings indicated that pretreatment with minocycline increased the expression level of CD206 but decreased that of IL-1β, while post-polarization treatment markedly decreased the expression level of both. Additionally, an in vitro migration assay revealed that minocycline exerts an inhibitory effect on macrophage migration. In brief, our study elucidates the effect of CCI-induced macrophage activation on neuropathic pain and provides new insights into the potential clinical application of minocycline for managing neuropathic pain.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978148","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":"4,4'-Dimethoxychalcone Mitigates Neuroinflammation Following Traumatic Brain Injury Through Modulation of the TREM2/PI3K/AKT/NF-κB Signaling Pathway.","authors":"Mengran Wang, Rui Zhao, Yue Su, Duhuan Zhai, Hengyan Liang, Lingkun Zhang, Weicheng Wang, Zhichun Wang, Min Qi, Xiaochun Jiang, Shizhang Ling, Guangfu Di","doi":"10.1007/s10753-025-02279-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02279-4","url":null,"abstract":"<p><p>Research on 4,4'-dimethoxychalcone (DMC) in the context of traumatic brain injury (TBI) is extremely limited, and no effective clinical treatments are available to improve outcomes for individuals with TBI. Our study aims to investigate the underlying mechanisms by which DMC may alleviate neuroinflammation and neuronal damage following TBI. This study seeks to provide a theoretical foundation for the development of future pharmacological therapies for TBI. A moderate TBI model was established using the fluid percussion injury (FPI) method. The recovery of neuromotor function following TBI was evaluated using the modified neurological severity score (mNSS), the Morris water maze test, and analysis of cerebral edema. Gene and protein expression levels were quantified using cell viability assays, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence. Network pharmacology was employed to predict potential targets of DMC, and gene ontology (GO) analysis along with KEGG pathway enrichment was conducted to predict signaling pathways affected by DMC.DMC treatment significantly improved neuromotor deficits in mice after TBI. In both in vivo and in vitro experiments, DMC suppressed microglial activation and decreased the production and release of inflammatory factors. Additionally, DMC reduced neuronal lesions after TBI. DMC notably decreased the elevated expression of triggering receptor expressed on myeloid cells 2 (TREM2) following TBI. Network pharmacological analysis indicated that DMC's therapeutic effects may be mediated through the PI3K/AKT signaling cascade. These findings indicate that DMC has therapeutic potential for TBI, with significant anti-inflammatory and neuroprotective properties likely mediated by the TREM2/PI3K/AKT/NF-κB signaling cascade.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990155","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":"Proteomic Profiles of Neutrophils from Behcet's Uveitis Patients and their Sex Differences.","authors":"Rong Liu, Qingfeng Wang, Qingyan Jiang, Rui Chang, Yan Zhou, Xingsheng Ye, Xiang Luo, Yujie Lai, Guannan Su, Peizeng Yang","doi":"10.1007/s10753-025-02305-5","DOIUrl":"https://doi.org/10.1007/s10753-025-02305-5","url":null,"abstract":"<p><p>Behcet's uveitis (BU) is one of the most vision-threatening uveitis entities with male-biased incidence and severity. Neutrophil dysfunction has been implicated in the pathogenesis of this disease. However, their proteomic changes are not completely understood. We performed proteomic analysis on peripheral neutrophils from patients with active BU and identified 82 up-regulated and 516 down-regulated differentially expressed proteins (DEPs) compared to healthy controls (HCs). We further performed functional analysis on these DEPs and found that the pathway involved in neutrophil extracellular trap formation was activated, whereas nucleotide metabolism and apoptosis were suppressed. Compared with female patients, male patients presented enhanced pathways associated neutrophil-mediated inflammatory responses and suppressed apoptosis. Additionally, integrative analysis of proteomic profiles and single-cell RNA sequencing (scRNA-seq) data revealed that these sex differences might be related to the enhanced inflammatory response in primed inflammatory and inflammatory neutrophils as well as deficiencies in apoptosis and nucleotide metabolism in ROS-responsive neutrophils. Collectively, our data revealed the proteomic profiles of neutrophils from patients with BU, and their functional changes may play crucial roles in the pathogenesis of this disease and its sex differences.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998879","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":"PTGS2 Silencing Inhibits Ferroptosis in Staphylococcus Aureus-induced Osteomyelitis By Blocking the IL-17A Signaling Pathway.","authors":"Si-Rui Zhou, Wen-Guang Li, Li-Dan Yang, Hao Xiang, Ying Jin, Jian-Bo Feng, Hua-Zhang Xiong, Jiachen Peng","doi":"10.1007/s10753-025-02296-3","DOIUrl":"https://doi.org/10.1007/s10753-025-02296-3","url":null,"abstract":"<p><strong>Objective: </strong>Osteomyelitis caused by Staphylococcus aureus (S. aureus) infection is an inflammatory bone disease characterized by continuous bone destruction, which is difficult to treat. This research aimed to explore the molecular mechanisms of S. aureus-induced osteomyelitis.</p><p><strong>Methods: </strong>Using the GSE166522 and GSE227521 datasets, hub differentially expressed genes (DEGs) were screened by bioinformatics analysis. Hub gene expression levels were validated in S. aureus-induced mouse models. An inhibitor of PTGS2, etoricoxib, was used to assess the role of PTGS2 in the osteomyelitis mouse model. PTGS2 was silenced in an LPS-induced MC3T3-E1 cell model to study its effect on cell function.</p><p><strong>Results: </strong>Six hub genes were screened, including ARG1, TIMP1, NOS2, PTGS2, SOCS3, and IL1B, highly expressed in the S. aureus-induced osteomyelitis model. Etoricoxib treatment attenuated the inflammatory infiltration of tibial tissue in mice with osteomyelitis. In vivo and in vitro, etoricoxib treatment and PTGS2 silencing reduced inflammatory factor (TNF-α, IL-1β, and IL-6) levels. PTGS2 silencing promoted LPS-induced MC3T3-E1 cell viability and inhibited apoptosis and ferroptosis. GPX4 and SLC7A11 protein levels were significantly increased after PTGS2 silencing. Mechanistically, IL-17A intervention significantly counteracted the impact of PTGS2 silencing on cell behaviors and secukinumab combined with PTGS2 silencing more effectively suppressed inflammation and ferroptosis, indicating that PTGS2 impeded the osteomyelitis progression by inhibiting the IL-17A pathway.</p><p><strong>Conclusion: </strong>Silencing PTGS2 reduces ferroptosis in S. aureus-induced osteomyelitis by obstructing the IL-17A pathway, which suggests a new approach for the treatment of osteomyelitis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982029","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}