title: A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.
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.
  
  
  RESULTS
  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 Cl(-) and HCO(3)(-), in mediating prostate HCO(3)(-) 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 HCO(3)(-) content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3)(-) on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3)(-) secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues.
  
  
  CONCLUSIONS
  The CFTR and its mediated HCO(3)(-) secretion may be up-regulated in prostatitis as a host defense mechanism.
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xie
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Tang
authors.forename: Wenming
authors.initials: W
authors.lastname: Xu
authors.forename: Ruiying
authors.initials: R
authors.lastname: Diao
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D001483:Base Sequence; D001639:Bicarbonates / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008969:Molecular Sequence Data; D011467:Prostate / Q000378:metabolism; D011472:Prostatitis / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
chemical_list: D000890:Anti-Infective Agents; D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D002256:Carbonic Anhydrases