{"title":"(-)-Epigallocatechin-3-gallate (EGCG) ameliorates ovalbumin-induced asthma by inhibiting inflammation via the TNF-α/TNF-R1/NLRP3 signaling pathway.","authors":"Beibei Zhang, Mengnan Zeng, Qimei Tie, Ru Wang, Mengya Wang, Yuanyuan Wu, Xiaoke Zheng, Weisheng Feng","doi":"10.1016/j.intimp.2024.113708","DOIUrl":"10.1016/j.intimp.2024.113708","url":null,"abstract":"<p><p>(-)-Epigallocatechin-3-gallate (EGCG) is a polyphenol in green tea with potential lung-protective effects. However, the effects of EGCG on airway inflammation in asthma remain unclear. The aim of this study was to investigate the effect and mechanism of EGCG on asthmatic airway inflammation. In this study, the therapeutic effects of EGCG on ovalbumin (OVA)-induced asthmatic mice were tested first. Second, the effects of EGCG on airway inflammation, airway hyperresponsiveness (AHR), airway mucus hypersecretion, cell apoptosis and differential genes were investigated. Finally, the relationships between the effects of EGCG on airway inflammation and the TNF-α/TNF-R1/NLRP3 signaling pathway in asthmatic mice were explored. The results showed that EGCG could attenuate AHR, alleviate the symptoms of alveolar wall thickening and inflammatory cell infiltration, decrease the levels of inflammatory cytokines and airway mucus markers, reduce apoptosis and reactive oxygen species (ROS) and increase the mitochondrial membrane potential (MMP) in primary lung cells in asthmatic mice. Additionally, EGCG significantly inhibited the activation of the TNF-α/TNF-R1/NLRP3 signaling pathway in the lung tissues of asthmatic mice. The lowest binding free energies of EGCG with TNF-α, TNF-R1 and NLRP3 were -11.6, -11.6 and -8.2 kcal/mol, respectively. Moreover, the equilibrium dissociation constant (KD) of EGCG and TNF-R1was 26.05 μmol/L. EGCG-mediated inhibition of TNF-α/TNF-R1/NLRP3 signaling pathway activation was blocked in LPS-induced BEAS-2B and RAW264.7 cells overexpressing TNF-α. Consequently, EGCG effectively attenuated AHR and inhibited airway inflammation and airway mucus hypersecretion in asthmatic mice, and these effects may be closely related to the TNF-α/TNF-R1/NLRP3 signaling pathway.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113708"},"PeriodicalIF":4.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768679","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":"Human leukocyte antigen DR alpha inhibits renal cell carcinoma progression by promoting the polarization of M2 macrophages to M1 via the NF-κB pathway.","authors":"Feng Xiong, Bowen Wang, Haoxun Zhang, Guoling Zhang, Yiwen Liu, Yujie Liu, Chunyang Wang","doi":"10.1016/j.intimp.2024.113706","DOIUrl":"10.1016/j.intimp.2024.113706","url":null,"abstract":"<p><p>Human leukocyte antigen DR alpha (HLA-DRA) is recognized for its inhibitory effect on the progression of clear cell renal cell carcinoma (ccRCC); high HLA-DRA expression levels are positively correlated with improved prognosis in patients with ccRCC. In this study, we evaluated HLA-DRA expression in ccRCCs, its effects on tumor-associated macrophage recruitment, and the influence of polarization. Clinical cohort analyses revealed that elevated HLA-DRA expression in ccRCC cells was correlated with enhanced tumor infiltration by M1-type macrophages. In addition, ccRCC prognosis was predicted by combining HLA-DRA expression level analysis and the M1/M2 macrophage ratio. In vitro studies demonstrated that ccRCC cells with increased HLA-DRA expression promoted THP-1 cell migration and induced macrophage polarization toward the M1 phenotype. The effect was further substantiated in a mouse xenograft model in which an increase in M1 macrophages was observed. In addition, co-culturing macrophages with the supernatant from cells overexpressing HLA-DRA induced the expression of proteins associated with both M1 and M2 macrophage polarization. HLA-DRA was intricately linked to the expression and secretion of chemokines, including CCL2, CCL5, MIP-1ɑ, and CXCL-10. Moreover, the NF-κB pathway activation promoted polarization to M1 macrophages. This study shows that HLA-DRA and the M1/M2 ratio are indicators of favorable prognosis in patients with ccRCC. HLA-DRA promotes M1-like polarization by regulating NF-κB, which can be used as a therapeutic target to enhance anti-tumor immunity.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113706"},"PeriodicalIF":4.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768680","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}
Fei Fei Hou, Jun Hao Mi, Qiong Wang, Yan Lin Tao, Shuai Bin Guo, Guang He Ran, Jing Chao Wang
{"title":"Macrophage polarization in sepsis: Emerging role and clinical application prospect.","authors":"Fei Fei Hou, Jun Hao Mi, Qiong Wang, Yan Lin Tao, Shuai Bin Guo, Guang He Ran, Jing Chao Wang","doi":"10.1016/j.intimp.2024.113715","DOIUrl":"10.1016/j.intimp.2024.113715","url":null,"abstract":"<p><p>Sepsis is a severe, potentially fatal condition defined by organ dysfunction due to excessive inflammation. Its complex pathogenesis and poor therapeutic outcomes pose significant challenges in treatment. Macrophages, with their high heterogeneity and plasticity, play crucial roles in both the innate and adaptive immune systems. They can polarize into M1-like macrophages, which promote pro-inflammatory responses, or M2-like macrophages, which mediate anti-inflammatory responses, positioning them as critical mediators in the immune response during sepsis.Macrophages are the main regulators of inflammatory responses, and their polarization is also regulated by inflammatory signaling pathways. This review highlights recent advances in the inflammatory signaling pathways involved in sepsis, mechanism of macrophage polarization mediated by inflammation-related signaling pathways in sepsis, and the role of signaling pathway mediated macrophage polarization in organ dysfunction involved in sepsis. We also explore the therapeutic potential of targeting macrophage polarization for immunotherapy, offering new perspectives on macrophage-targeted treatments for sepsis.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113715"},"PeriodicalIF":4.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768681","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}
Shuhui Wang, Zheng Huang, Shangshu Nie, Yu Chen, Yu Lei, Wei Tu, Min Luo, Zhen-Gang Zhang, De-An Tian, Jin Gong, Mei Liu
{"title":"Unveiling the interplay between hepatocyte SATB1 and innate immunity in autoimmune hepatitis.","authors":"Shuhui Wang, Zheng Huang, Shangshu Nie, Yu Chen, Yu Lei, Wei Tu, Min Luo, Zhen-Gang Zhang, De-An Tian, Jin Gong, Mei Liu","doi":"10.1016/j.intimp.2024.113712","DOIUrl":"10.1016/j.intimp.2024.113712","url":null,"abstract":"<p><strong>Background: </strong>Investigating the function of SATB1 in hepatocytes is essential for developing therapeutic strategies for autoimmune hepatitis (AIH). Although SATB1 has been extensively studied in immune cells, its specific activity in hepatocytes within the context of AIH remains unclear.</p><p><strong>Methods: </strong>SATB1 expression in AIH hepatocytes was assessed by qRT-PCR, Western blotting, flow cytometry, and immunohistochemistry. In vivo modulation used RNA interference viruses and overexpression plasmids. SATB1's proinflammatory effects were analyzed with protein microarray, immunohistochemistry, and flow cytometry. Chemotactic effects on RAW264.7 macrophages were tested in vitro, with mechanisms explored by dual-luciferase assays and CUT&RUN qPCR. Liver injury was evaluated by histopathology and serum biochemistry.</p><p><strong>Results: </strong>SATB1 was significantly upregulated in hepatocytes of AIH patients and models, showing a stronger increase in hepatocytes than in CD45<sup>+</sup> cells, and positively correlated with liver injury severity. In vivo RNAi-mediated SATB1 inhibition reduced liver inflammation, while SATB1 overexpression aggravated AIH progression. Both interference and overexpression experiments confirmed that SATB1 promotes liver injury by facilitating the infiltration of proinflammatory (Ly6C<sup>high</sup>) macrophage. In vitro, supernatant from SATB1-overexpressing hepatocytes enriched chemokine signaling pathways, leading to increased CCL2 expression and release, which attracted macrophages and drove their proinflammatory polarization. Mechanistically, SATB1 promoted CCL2 transcription by binding to its DNA and recruiting p300/CBP.</p><p><strong>Conclusions: </strong>This study reveals that SATB1 is upregulated in hepatocytes in AIH. Elevated SATB1 levels in liver cells contribute to autoimmune hepatitis by increasing CCL2 expression, promoting the recruitment of inflammatory monocyte-derived macrophage, and reshaping the composition of the liver immune microenvironment.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113712"},"PeriodicalIF":4.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768682","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}
Salvatore Chirumbolo, Marianno Franzini, Umberto Tirelli, Luigi Valdenassi
{"title":"The use of ozone in the anti-aging and wellbeing proposals. A proof of concern.","authors":"Salvatore Chirumbolo, Marianno Franzini, Umberto Tirelli, Luigi Valdenassi","doi":"10.1016/j.intimp.2024.113609","DOIUrl":"10.1016/j.intimp.2024.113609","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113609"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695578","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}
Jing Zuo, Die Wu, Ying Zhang, Huan Luo, Guoqing Jing, Min Yuan, Qing Fang, Cheng Yang, Xing Wang, Xiaojing Wu, Xuemin Song
{"title":"VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages.","authors":"Jing Zuo, Die Wu, Ying Zhang, Huan Luo, Guoqing Jing, Min Yuan, Qing Fang, Cheng Yang, Xing Wang, Xiaojing Wu, Xuemin Song","doi":"10.1016/j.intimp.2024.113622","DOIUrl":"10.1016/j.intimp.2024.113622","url":null,"abstract":"<p><p>Macrophages are present in all tissues and body compartments under homeostatic physiological conditions. Importantly, they play a key role in pathological inflammatory processes when disturbed. They can quickly produce large amounts of inflammatory cytokines in response to danger signals. Macrophages can recognize muramyl dipeptide (MDP) through nucleotide-binding oligomerization domain (NOD)-like receptors, subsequently activating the NF-κB signaling pathway and producing proinflammatory cytokines. Erbin can bind to NOD2 and inhibit MDP-induced NF-κB activation, thus participating in the regulation of inflammatory response. Stabilizing or enhancing Erbin expression is essential for suppressing inflammatory responses. In this study, we used a deubiquitination enzyme plasmid library to screen for a key deubiquitinase, VCPIP1, which interacts with Erbin and influences its stability through deubiquitination modification. We investigated whether VCPIP1 affects inflammation using MDP-stimulated RAW 264.7 and BMDMs cells. The results showed that VCPIP1 deficiency reduced Erbin expression and increased NF-κB phosphorylation. Additionally, VCPIP1 deficiency promoted the release of inflammatory factors (IL-1β, IL-6, and TNF-α) in RAW 264.7 cells and BMDMs. This study further expands the role of deubiquitinases (DUBs) in inflammation, providing new insights for the prevention and treatment of sepsis, tumors, immune diseases, and other inflammatory reactions.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 3","pages":"113622"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647991","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 emerging role of microglia in the development and therapy of multiple sclerosis.","authors":"Yunrong Nan, Shuting Ni, Mei Liu, Kaili Hu","doi":"10.1016/j.intimp.2024.113476","DOIUrl":"10.1016/j.intimp.2024.113476","url":null,"abstract":"<p><p>Microglia are innate immune cells that maintain homeostasis of the central nervous system (CNS) and affect various neurodegenerative diseases, especially multiple sclerosis (MS). MS is an autoimmune disease of the CNS characterized by persistent inflammation, diffuse axonal damage, and microglia activation. Recent studies have shown that microglia are extremely related to the pathological state of MS and play an important role in the development of MS. This article reviews the multiple roles of microglia in the progression of MS, including the regulatory role of microglia in inflammation, remyelination, oxidative stress, the influence of phagocytosis and antigen-presenting capacity of microglia, and the recent progress by using microglia as a target for MS therapy. Microglia modulation may be a potential way for better MS therapy.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 2","pages":"113476"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545316","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}