Fei Sun, Jingwei Wang, Xiangfen Ji, Zhenli Wang, Shuai Gao, Kai Wang
{"title":"CCL25是D-Gal/LPS诱导的急性肝衰竭的发病机制之一。","authors":"Fei Sun, Jingwei Wang, Xiangfen Ji, Zhenli Wang, Shuai Gao, Kai Wang","doi":"10.1111/jgh.16732","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and aim: </strong>Acute liver failure (ALF) is a fatal clinical syndrome of severe hepatic dysfunction. Chemokines promote liver diseases by recruiting and activating immune cells. We aimed to investigate the role of C-C chemokine ligand 25 (CCL25) in ALF.</p><p><strong>Methods: </strong>An ALF mouse model induced by D-galactosamine/lipopolysaccharide was evaluated through liver hematoxylin and eosin staining and serum transaminase and cytokine measurement. CCL25 expression in serum was analyzed by ELISA and in liver by immunohistochemical staining and western blot. C-C chemokine receptor 9 (CCR9)-expressing cells in the liver were identified by immunofluorescence staining. The effects of anti-CCL25 on ALF were evaluated in vivo. Cytokine expression and migration of CCL25-stimulated RAW264.7 macrophages were studied. We also investigated the role of anti-CCL25 and BMS-345541, an NF-κB signaling inhibitor, in vitro. NF-κB activation was assessed via western blot, and p65 nuclear translocation was detected using cellular immunofluorescence.</p><p><strong>Results: </strong>ALF mice showed severe histological damage and high serum levels of aminotransferase and inflammatory cytokines. Elevated CCL25 and NF-κB activation was observed in vivo. CCR9 was expressed on macrophages in ALF mouse liver. ALF was suppressed after anti-CCL25 treatment, with significant NF-κB inhibition. In vitro, CCL25 induced strong migration and cytokine release in RAW264.7 macrophages, which were eliminated by anti-CCL25 and BMS-345541. Furthermore, the NF-κB activation and p65 nuclear translocation induced by CCL25 were also inhibited by anti-CCL25 and BMS-345541.</p><p><strong>Conclusion: </strong>CCL25 contributes to ALF development by inducing macrophage-mediated inflammation via activation of the NF-κB signaling.</p>","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CCL25 contributes to the pathogenesis of D-Gal/LPS-induced acute liver failure.\",\"authors\":\"Fei Sun, Jingwei Wang, Xiangfen Ji, Zhenli Wang, Shuai Gao, Kai Wang\",\"doi\":\"10.1111/jgh.16732\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and aim: </strong>Acute liver failure (ALF) is a fatal clinical syndrome of severe hepatic dysfunction. Chemokines promote liver diseases by recruiting and activating immune cells. We aimed to investigate the role of C-C chemokine ligand 25 (CCL25) in ALF.</p><p><strong>Methods: </strong>An ALF mouse model induced by D-galactosamine/lipopolysaccharide was evaluated through liver hematoxylin and eosin staining and serum transaminase and cytokine measurement. CCL25 expression in serum was analyzed by ELISA and in liver by immunohistochemical staining and western blot. C-C chemokine receptor 9 (CCR9)-expressing cells in the liver were identified by immunofluorescence staining. The effects of anti-CCL25 on ALF were evaluated in vivo. Cytokine expression and migration of CCL25-stimulated RAW264.7 macrophages were studied. We also investigated the role of anti-CCL25 and BMS-345541, an NF-κB signaling inhibitor, in vitro. NF-κB activation was assessed via western blot, and p65 nuclear translocation was detected using cellular immunofluorescence.</p><p><strong>Results: </strong>ALF mice showed severe histological damage and high serum levels of aminotransferase and inflammatory cytokines. Elevated CCL25 and NF-κB activation was observed in vivo. CCR9 was expressed on macrophages in ALF mouse liver. ALF was suppressed after anti-CCL25 treatment, with significant NF-κB inhibition. In vitro, CCL25 induced strong migration and cytokine release in RAW264.7 macrophages, which were eliminated by anti-CCL25 and BMS-345541. Furthermore, the NF-κB activation and p65 nuclear translocation induced by CCL25 were also inhibited by anti-CCL25 and BMS-345541.</p><p><strong>Conclusion: </strong>CCL25 contributes to ALF development by inducing macrophage-mediated inflammation via activation of the NF-κB signaling.</p>\",\"PeriodicalId\":15877,\"journal\":{\"name\":\"Journal of Gastroenterology and Hepatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gastroenterology and Hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/jgh.16732\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gastroenterology and Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/jgh.16732","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
CCL25 contributes to the pathogenesis of D-Gal/LPS-induced acute liver failure.
Background and aim: Acute liver failure (ALF) is a fatal clinical syndrome of severe hepatic dysfunction. Chemokines promote liver diseases by recruiting and activating immune cells. We aimed to investigate the role of C-C chemokine ligand 25 (CCL25) in ALF.
Methods: An ALF mouse model induced by D-galactosamine/lipopolysaccharide was evaluated through liver hematoxylin and eosin staining and serum transaminase and cytokine measurement. CCL25 expression in serum was analyzed by ELISA and in liver by immunohistochemical staining and western blot. C-C chemokine receptor 9 (CCR9)-expressing cells in the liver were identified by immunofluorescence staining. The effects of anti-CCL25 on ALF were evaluated in vivo. Cytokine expression and migration of CCL25-stimulated RAW264.7 macrophages were studied. We also investigated the role of anti-CCL25 and BMS-345541, an NF-κB signaling inhibitor, in vitro. NF-κB activation was assessed via western blot, and p65 nuclear translocation was detected using cellular immunofluorescence.
Results: ALF mice showed severe histological damage and high serum levels of aminotransferase and inflammatory cytokines. Elevated CCL25 and NF-κB activation was observed in vivo. CCR9 was expressed on macrophages in ALF mouse liver. ALF was suppressed after anti-CCL25 treatment, with significant NF-κB inhibition. In vitro, CCL25 induced strong migration and cytokine release in RAW264.7 macrophages, which were eliminated by anti-CCL25 and BMS-345541. Furthermore, the NF-κB activation and p65 nuclear translocation induced by CCL25 were also inhibited by anti-CCL25 and BMS-345541.
Conclusion: CCL25 contributes to ALF development by inducing macrophage-mediated inflammation via activation of the NF-κB signaling.
期刊介绍:
Journal of Gastroenterology and Hepatology is produced 12 times per year and publishes peer-reviewed original papers, reviews and editorials concerned with clinical practice and research in the fields of hepatology, gastroenterology and endoscopy. Papers cover the medical, radiological, pathological, biochemical, physiological and historical aspects of the subject areas. All submitted papers are reviewed by at least two referees expert in the field of the submitted paper.