title: Enhancement of the innate immune response of bladder epithelial cells by Astragalus polysaccharides through upregulation of TLR4 expression.
abstract: The innate host defenses at mucosal surfaces are critical in the early stages of urinary tract bacterial infection. Recent studies have shown that uroepithelial cells aid innate immune cells in fighting off infection, although the exact mechanism by which the uroepithilium participates in immunity remains unclear. TLR4 has been implicated to possess antimicrobial activities specific for bladder epithelial cells (BECs). TLR4 promotes secretion of IL-6 and IL-8, mediates inhibition of bladder epithelial cell (BEC) bacterial invasion, and mediates expulsion of uropathogenic Escherichia coli from BECs. In this study, cultured 5637 cells and Balb/C mice were treated with Astragalus polysaccharides (APS) against invading E. coli. To determine the contribution of TLR4 upregulation to immune response, TLR4 expression and bacterial colony numbers were monitored. After 24 h incubation, only 5637 cells treated with 500 microg/ml APS expressed higher levels of TLR4 compared with the untreated group. However, after 48h, all 5637 cells treated by APS showed higher levels of TLR4 expression than the control cells. The TLR4 expression in the bladder and macrophages mice that received APS was higher than that in the controls. Bacterial colonization in 5637 cells and the bladders of mice treated with APS was significantly reduced compared with the controls. These results demonstrate that at certain concentrations, APS can induce increased TLR4 expression in vivo and in vitro. Further, TLR4 expression upregulation can enhance innate immunity during mucosal bacterial infection. The findings establish the use of APS to modulate the innate immune response of the urinary tract through TLR4 expression regulation as an alternative option for UTI treatment.
authors.affiliation: Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province 610041, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yin
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianling
authors.initials: J
authors.lastname: Yang
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Ma
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Yao
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D015854:Up-Regulation; D001743:Urinary Bladder / Q000187:drug effects* / Q000276:immunology; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000276:immunology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D011134:Polysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4