InflammationPub Date : 2025-08-01Epub Date: 2024-12-18DOI: 10.1007/s10753-024-02194-0
Chenfeng Shou, Yuansong Sun, Qiao Zhang, Wenqiang Zhang, Qi Yan, Tao Xu, He Li
{"title":"S100A9 Inhibition Mitigates Acute Pancreatitis by Suppressing RAGE Expression and Subsequently Ameliorating Inflammation.","authors":"Chenfeng Shou, Yuansong Sun, Qiao Zhang, Wenqiang Zhang, Qi Yan, Tao Xu, He Li","doi":"10.1007/s10753-024-02194-0","DOIUrl":"10.1007/s10753-024-02194-0","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a common acute inflammatory abdominal condition. Severe acute pancreatitis (SAP) can provoke a systemic inflammatory response and lead to multiple organ failure. The S100A9 protein, recognized as a major inflammatory biomarker, plays a significant role in both infection and inflammatory responses. Despite its known role in inflammation, the precise role of S100A9 in AP remains poorly understood. This study aimed to elucidate the potential role of S100A9 in AP and investigate the underlying mechanism. We employed a mouse model of AP and the AR42J cell line to investigate the functional role of S100A9. The effect of S100A9 on pancreatic injury and the expression of inflammatory factors (IL-6, IL-1β, and TNF-α) was assessed through targeted inhibition of S100A9 expression in the mouse model of AP. Furthermore, the modulatory effect of cerulein-induced inflammatory responses on AR42J cells was assessed after adding the S100A9 recombinant protein. In the mouse model of AP, targeted inhibition of S100A9 markedly ameliorated pancreatic injury and significantly decreased the expression levels of IL-6, IL-1β, and TNF-α. Moreover, increased levels of S100A9 were positively correlated with elevated expression of receptor for advanced glycation endproducts (RAGE) in pancreatic acinar cells. In AR42J cells, the introduction of S100A9 recombinant protein enhanced RAGE expression and exacerbated cerulein-induced inflammatory response. S100A9 inhibition significantly alleviated the pancreatic inflammatory response by downregulating RAGE expression, thereby improving AP.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2355-2366"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846607","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":"Critical Role of S100A9 in Sepsis-associated Acute Kidney Injury: Mechanistic Insights through Pyroptosis Pathway Modulation.","authors":"Jian-Nan Zhang, Rui Gong, Yi-Qi Wang, Yang Chong, Quan-Kuan Gu, Ming-Bo Zhao, Ping Huang, Yu-Cheng Qi, Xiang-Lin Meng, Ming-Yan Zhao","doi":"10.1007/s10753-024-02161-9","DOIUrl":"10.1007/s10753-024-02161-9","url":null,"abstract":"<p><p>This study investigates the role of S100A9 in sepsis-associated AKI (SA-AKI) through the lens of pyroptosis, a controlled form of cell death mediated by the gasdermin protein family. Using C57BL/6 mice and S100A9 knockout mice subjected to cecal ligation and puncture (CLP), RNA sequencing and bioinformatics analyses revealed differentially expressed genes (DEGs) related to inflammation and immune responses, with notable upregulation of S100A9. Functional enrichment analyses (GO and KEGG) indicated these DEGs are involved in interferon-beta response, immune processes, and cell adhesion. Protein-protein interaction (PPI) network analyses further emphasized S100A9's pivotal role in SA-AKI.Clinical validation measured S100A9 levels in serum and urine samples from SA-AKI patients and healthy volunteers, finding elevated S100A9 levels in the former. In vivo experiments showed that S100A9 knockout mice exhibited reduced kidney injury and inflammation, indicated by lower serum creatinine, urea nitrogen, and inflammatory markers (IL-1β and IL-18). Histopathological analyses and immunohistochemistry confirmed less renal damage and reduced expression of cleaved IL-1β and GSDMD-N in S100A9-deficient mice. Electron microscopy and Western blotting validated that S100A9 deficiency mitigates caspase-1-dependent pyroptosis.Cellular experiments with HK-2 cells demonstrated that S100A9 knockdown alleviated LPS-induced cell damage and reduced pyroptosis markers. These findings illuminate S100A9's involvement in NLRP3 inflammasome activation and pyroptosis, suggesting potential therapeutic targets for SA-AKI. Targeting S100A9 may offer new therapeutic avenues, improving outcomes for sepsis-related kidney injury patients. Future research should aim to validate these findings in larger clinical settings.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1879-1899"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400162","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}
InflammationPub Date : 2025-08-01Epub Date: 2024-11-12DOI: 10.1007/s10753-024-02183-3
Levi Hoste, Bram Meertens, Benson Ogunjimi, Vito Sabato, Khadija Guerti, Jeroen van der Hilst, Jeroen Bogie, Rik Joos, Karlien Claes, Veronique Debacker, Fleur Janssen, Simon J Tavernier, Peggy Jacques, Steven Callens, Joke Dehoorne, Filomeen Haerynck
{"title":"Identification of a 5-Plex Cytokine Signature that Differentiates Patients with Multiple Systemic Inflammatory Diseases.","authors":"Levi Hoste, Bram Meertens, Benson Ogunjimi, Vito Sabato, Khadija Guerti, Jeroen van der Hilst, Jeroen Bogie, Rik Joos, Karlien Claes, Veronique Debacker, Fleur Janssen, Simon J Tavernier, Peggy Jacques, Steven Callens, Joke Dehoorne, Filomeen Haerynck","doi":"10.1007/s10753-024-02183-3","DOIUrl":"10.1007/s10753-024-02183-3","url":null,"abstract":"<p><p>Patients with non-infectious systemic inflammation may suffer from one of many diseases, including hyperinflammation (HI), autoinflammatory disorders (AID), and systemic autoimmune disease (AI). Despite their clinical overlap, the pathophysiology and patient management differ between these disorders. We aimed to investigate blood biomarkers able to discriminate between patient groups. We included 44 patients with active clinical and/or genetic systemic inflammatory disease (9 HI, 27 AID, 8 systemic AI) and 16 healthy controls. We quantified 55 serum proteins and combined multiple machine learning algorithms to identify five proteins (CCL26, CXCL10, ICAM-1, IL-27, and SAA) that maximally separated patient groups. High ICAM-1 was associated with HI. AID was characterized by an increase in SAA and decrease in CXCL10 levels. A trend for higher CXCL10 and statistically lower SAA was observed in patients with systemic AI. Principal component analysis and unsupervised hierarchical clustering confirmed separation of disease groups. Logistic regression modelling revealed a high statistical significance for HI (P = 0.001), AID, and systemic AI (P < 0.0001). Predictive accuracy was excellent for systemic AI (AUC 0.94) and AID (0.91) and good for HI (0.81). Further research is needed to validate findings in a larger prospective cohort. Results will contribute to a better understanding of the pathophysiology of systemic inflammatory disorders and can improve diagnosis and patient management.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2182-2197"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619377","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":"Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism.","authors":"Yang Wang, Xiaogang Qin, Jinhao Shuai, Xiayun Wan, Duonan Yu, Ling Ling, Qianwen Lu, Mengying Lv","doi":"10.1007/s10753-024-02182-4","DOIUrl":"10.1007/s10753-024-02182-4","url":null,"abstract":"<p><p>Pristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2166-2181"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619379","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}
InflammationPub Date : 2025-08-01Epub Date: 2025-02-04DOI: 10.1007/s10753-024-02231-y
Solana Capalbo, Annabella Polyakova, Zayd El Imane, Izza Khan, Toshihisa Kawai, Satoru Shindo, Manuel Salinas
{"title":"A Comprehensive Review of Contemporary Bioreactors for Vascular Inflammation Studies.","authors":"Solana Capalbo, Annabella Polyakova, Zayd El Imane, Izza Khan, Toshihisa Kawai, Satoru Shindo, Manuel Salinas","doi":"10.1007/s10753-024-02231-y","DOIUrl":"10.1007/s10753-024-02231-y","url":null,"abstract":"<p><p>The field of vascular biology has advanced significantly with bioreactor systems, which have become essential tools for investigating the mechanisms of vascular inflammatory diseases such as atherosclerosis, vasculitis, and aneurysms. These bioreactors allow researchers to recreate specific vascular environments, providing a controlled setting for studying the effects of blood flow, mechanical stress, and biochemical factors on vascular tissues. Through these systems, researchers can explore how physical and chemical cues contribute to disease processes and cellular responses, enhancing our understanding of disease progression. Bioreactor studies have demonstrated that hemodynamic forces, particularly shear stress, influence endothelial cell behavior and play a role in vascular pathologies. For instance, in atherosclerosis, disturbed flow patterns are associated with endothelial dysfunction and plaque development. By simulating these conditions, bioreactors provide insight into the effects of mechanical forces on vascular wall biology, highlighting how altered flow can contribute to disease. Bioreactors also support studies on the impacts of pulsatile flow and circumferential stress, allowing a closer approximation of physiological environments. Beyond flow dynamics, these systems facilitate investigation into how vascular cells respond to biochemical signals, inflammatory markers, and therapeutic interventions. This integrated approach allows for a more complete picture of the factors involved in vascular disease. Recent advancements, such as vessel-on-a-chip models and artery-mimicking setups, extend the capabilities of bioreactors by enabling researchers to model a broader range of conditions relevant to human physiology. In vasculitis studies, bioreactors help explore immune interactions with endothelial cells, especially with stem cell-derived cells that replicate patient-specific responses. Bioreactors also play a role in vascular tissue engineering, particularly in assessing materials and scaffold-free designs that may reduce inflammation in vascular grafts. These efforts contribute to the ongoing search for more compatible graft materials, with the potential to improve outcomes in clinical applications. This review provides a comprehensive overview of bioreactor technologies applied in vascular inflammation research, examining their designs, applications, and contributions to disease modeling. Organized into sections on bioreactor configurations, flow dynamics, biochemical interactions, and tissue engineering applications, the review concludes by discussing recent innovations and highlighting directions for future research, underscoring the role of bioreactors in bridging laboratory studies with insights into vascular disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1624-1659"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189056","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}
InflammationPub Date : 2025-08-01Epub Date: 2024-10-23DOI: 10.1007/s10753-024-02153-9
Yuming Liu, Zhigang Liu, Xiaohe Li, Wenqi Li, Zhongyi Yang, Ran Jiao, Qing Wang, Lingxin Meng, Tiantian Zhang, Jing Liu, Dan Chai, Na Zhang, Shouchun Peng, Honggang Zhou, Cheng Yang
{"title":"Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-β1 Pathway.","authors":"Yuming Liu, Zhigang Liu, Xiaohe Li, Wenqi Li, Zhongyi Yang, Ran Jiao, Qing Wang, Lingxin Meng, Tiantian Zhang, Jing Liu, Dan Chai, Na Zhang, Shouchun Peng, Honggang Zhou, Cheng Yang","doi":"10.1007/s10753-024-02153-9","DOIUrl":"10.1007/s10753-024-02153-9","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common complication of SSc and a major contributor to SSc-related deaths. Besides nintedanib and tocilizumab, there are currently no clinically approved drugs for SSc-ILD, highlighting the urgent need for new treatment strategies. Previous studies have shown that cyclic adenosine monophosphate (cAMP) plays a crucial role in the pathogenesis of SSc and lung fibrosis. Phosphodiesterases (PDEs) are enzymes that specifically hydrolyze cAMP, making PDE inhibitors promising candidates for SSc-ILD treatment. Nerandomilast, a preferential phosphodiesterase 4B (PDE4B) inhibitor currently undergoing phase III clinical trials for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases (PF-ILD), has good preference for PDE4B but lacks studies for SSc-ILD. Our research demonstrates that nerandomilast effectively inhibits skin and lung fibrosis in a bleomycin-induced mouse model of SSc-ILD. For lung fibrosis, we found that nerandomilast could improve bleomycin-induced SSc-ILD through inhibiting PDE4B and the TGF-β1-Smads/non-Smads signaling pathways, which provides a theoretical basis for potential therapeutic drug development for SSc-ILD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1760-1774"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499560","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}
InflammationPub Date : 2025-08-01Epub Date: 2024-11-06DOI: 10.1007/s10753-024-02175-3
Jian Zeng, Xiao-Long Du, Qiong-Qiong Lu, Wan-Qun Chen, Xiao-Jun Yang
{"title":"Inhibition of GDNF-Driven Macrophage-to-Myofibroblast Transition Protects Against Colitis-Associated Intestinal Fibrosis.","authors":"Jian Zeng, Xiao-Long Du, Qiong-Qiong Lu, Wan-Qun Chen, Xiao-Jun Yang","doi":"10.1007/s10753-024-02175-3","DOIUrl":"10.1007/s10753-024-02175-3","url":null,"abstract":"<p><p>Glial cell line-derived neurotrophic factor (GDNF) has been demonstrated to promote the development of liver fibrosis, but its role in intestinal fibrosis is unknown. Macrophage-to-myofibroblast transition (MMT) is an important pathway contributing to fibrosis diseases. However, whether MMT cells, characterized by co-expressing both macrophage (CD68 or F4/80) and myofibroblast (α-SMA) markers, occurs in intestinal fibrosis remain to be addressed. Here, we showed that GDNF expression and the infiltration of MMT cells in intestinal tissues from patients with fibrostenotic Crohn's disease (CD) and a mouse model of chronic dextran sodium salt-induced intestinal fibrosis were significantly increased. GDNF induced bone marrow-derived macrophages (BMDMs) differentiation into MMT cells in vitro. Mechanistically, the Src pathway was activated by GDNF stimulation and contributed to GDNF-induced MMT in BMDMs. Moreover, pharmacological inhibition of GDNF by using antibody markedly decreased the infiltration of MMT cells following the decrease of collagen deposition and α-SMA and Col1 expression in the mouse model of colitis-associated intestinal fibrosis. In conclusion, GDNF is able to induce MMT and contributes to intestinal fibrosis in the context of chronic intestinal inflammation. Pharmacological inhibition of GDNF-driven MMT might provide a novel approach for the treatment of fibrosis complication in CD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2069-2077"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583124","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":"5-Aminolevulinic Acid (5-ALA) Plays an Important Role in the Function of Innate Immune Cells.","authors":"Shinichi Saitoh, Yuji Takeda, Akemi Araki, Yusuke Nouchi, Risako Yamaguchi, Osamu Nakajima, Hironobu Asao","doi":"10.1007/s10753-024-02212-1","DOIUrl":"10.1007/s10753-024-02212-1","url":null,"abstract":"<p><p>5-aminolevulinic acid (5-ALA) is an amino acid essential for the synthesis of heme, which is important for various cellular functions, including the mitochondrial electron transport chain. We previously established heterozygous knockout mice (Alas1<sup>+/-</sup>) for 5-ALA synthase 1 (ALAS1), the rate-limiting enzyme for 5-ALA synthesis, and reported that the mice developed non-obese insulin-resistant diabetes. In the present study, we used these mice to analyze the role of 5-ALA in the immune system. Using a lipopolysaccharide (LPS)-induced septic shock model, Alas1<sup>+/-</sup> mice showed reduced mortality compared to wild-type (WT) mice. In this model experiment, the plasma concentration of inflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6), and the chemokine monocyte chemoattractant protein-1 (MCP1) decreased in Alas1<sup>+/-</sup> mice compared that in WT mice, and inflammatory cell infiltration into the peritoneal cavity was also decreased. In ex vivo experiments, exogenous 5-ALA pretreatment enhanced LPS-induced TNFα and IL-6 production from peripheral blood leukocytes of Alas1<sup>+/-</sup> mice. Additionally, 5-ALA pretreatment enhanced LPS-induced activation of inflammatory cytokine genes in innate immune cells. Interestingly, the phagocytosis and reactive oxygen species (ROS) producing abilities of neutrophils were clearly hampered in Alas1<sup>+/-</sup> mice compared to WT mice, but after 2 weeks of 5-ALA administration to Alas1<sup>+/-</sup> mice, both abilities were significantly recovered up to the level in WT mice. These results reveal that 5-ALA is essential for the function of innate immune cells. Because 5-ALA can be supplemented orally, it has the potential to be used as a drug to restore innate immune function.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2588-2599"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864245","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}
InflammationPub Date : 2025-08-01Epub Date: 2024-12-09DOI: 10.1007/s10753-024-02196-y
Jiaqi Li, Gang Liu
{"title":"Lentiviral Injection of Inter-α-Trypsin Inhibitor Heavy Chain 4 Promotes Female Spinal Cord Injury Mice Recuperation by Diminishing Peripheral and Central Inflammation.","authors":"Jiaqi Li, Gang Liu","doi":"10.1007/s10753-024-02196-y","DOIUrl":"10.1007/s10753-024-02196-y","url":null,"abstract":"<p><p>Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) acts as a mediator of inflammation and extracellular matrix stabilization. The current study intended to delve into the impact of ITIH4 on locomotor performance, nerve injury, neuroinflammation, systemic inflammation, and the downstream pathway in spinal cord injury (SCI) mice. Overexpression lentivirus of ITIH4 (LV-ITIH4) and negative control lentivirus (LV-NC) were intravenously injected into adult C57BL/6 mice on 7 days before SCI surgery. All mice were euthanized on day 28 after SCI surgery, and their blood samples and spinal cord tissues were collected. Decreased relative gene expression and protein levels of ITIH4 were observed in SCI mice. LV-ITIH4 improved the locomotor performance compared to LV-NC in SCI mice. In spinal cord of SCI mice, LV-ITIH4 reduced apoptosis and increased survival of neurons compared to LV-NC. By comparison with LV-NC, LV-ITIH4 also reduced relative gene expressions of interleukin (IL)-6 and tumor necrosis factor-α in spinal cord of SCI mice. Moreover, LV-ITIH4 reduced microglia M1 polarization compared with LV-NC in spinal cord of SCI mice. In the serum, LV-ITIH4 decreased the protein levels of IL-6 and IL-1β compared to LV-NC in SCI mice. LV-ITIH4 also inhibited the nuclear factor kappa-B (NF-κB) pathway compared to LV-NC in spinal cord of SCI mice. ITIH4 enhances locomotor performance in SCI mice, and it inhibits nerve injury, neuroinflammation, systemic inflammation, and the NF-κB pathway in SCI mice.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2387-2394"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794686","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}