title: Astragaloside IV alleviates E. coli-caused peritonitis via upregulation of neutrophil influx to the site of infection.
abstract: Astragaloside IV (AS-IV), an active saponin purified from Astragali Radix, has been identified with broad biological and pharmacological activities. In the present study, we continue to explore the potential effect of AS-IV on antibacterial response using an acute E. coli peritoneal infection model. Our findings implied that administration of AS-IV decreases mortality in mice challenged by lethal E. coli infection. The protection of AS-IV was related to promotion of neutrophil extravasation into the peritoneum and bacterial clearance. Toll-like receptor (TLR) activation in neutrophils has been reported to reduce CXCR2 expression and subsequent neutrophil migration. Our data indicated that AS-IV prevented the reduction of CXCR2 expression and neutrophil migration induced by LPS, the activator for TLR4. Moreover, we found that AS-IV blocks LPS-induced suppression of CXCR2 on neutrophils by inhibiting the expression of G protein-coupled receptor kinase-2 (GRK2), an agonist that regulates desensitization and internalization of chemokine receptors. Taken together, these data propose that AS-IV, through modulating GRK2-CXCR2 signal in neutrophils, offers an essential efficacy on host antibacterial immunity.
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Baohong
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Intensive Care Unit, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Dai
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: lyjche@163.com.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: huiyin0103@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D027885:Astragalus propinquus / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010538:Peritonitis / Q000188:drug therapy*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000627:therapeutic use*; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D008070:Lipopolysaccharides; D023063:Receptors, Interleukin-8B; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2
keywords: Astragaloside IV; CXCR2; Migration; Neutrophils; Peritonitis