a host defense mechanism involving cftr-mediated bicarbonate secretion in bacterial prostatitis宿主防御机制涉及cftr-mediated碳酸氢盐分泌在细菌性前列腺炎.pdfVIP

A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis 1 1 2 3 3 1,2 Chen Xie , Xiaoxiao Tang , Wenming Xu , Ruiying Diao , Zhiming Cai , Hsiao Chang Chan * 1 Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China, 2 The Chinese University of Hong Kong Joint Laboratory of Reproductive Medicine, Sichuan University, West China Second University Hospital, Hong Kong, China, 3 Guangdong Key Laboratory of Male Reproduction and Genetics, Peking University Shenzhen Hospital, Shenzhen, China Abstract Background: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. Methodology/Principal Findings: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl2 and HCO32, in mediating prostate HCO32 secretion and its possible role in bacterial killing. Upon Escherichia coli (E coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO32 content (.50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO32 on bacterial killing was confirmed by its ability to increase cAM