Uropathogenic Escherichia coli-induced inflammation alters mouse urinary bladder contraction via an interleukin-6-activated inducible nitric oxide synthase-related pathway.
Escherichia coli is the most common cause of urinary tract infection. Elevated blood and urine interleukin-6 (IL-6) levels have been shown in inflammatory urinary tract diseases. The role of IL-6 in mediating the urodynamic dysfunction in response to E. coli-induced urinary tract infection has not yet been fully elucidated. In this study, we investigated the role of IL-6 in the nitric oxide (NO)-triggered alteration of contractile responses in the urinary bladder under an E. coli-induced inflammatory condition. The electrical field stimulation (EFS)-evoked contractions of the isolated detrusor strips, and immunoblotting for detecting protein expression in the bladders was measured short term (1 h) or long term (6 or 24 h) after intraperitoneal injection of E. coli endotoxin (lipopolysaccharide [LPS]) or intravesical instillation of human pyelonephritogenic E. coli-J96 (O4:K6) strain or LPS into mice. IL-6 and NO productions were increased in the urinary bladders of mice 1 to 24 h after LPS or E. coli-J96 treatment. Inducible NO synthase (iNOS) expression and protein kinase C (PKC) activation and EFS-evoked detrusor contractions were increased in the bladders at 6 h after LPS or E. coli-J96 treatment, which could be reversed by anti-IL-6 antibody and iNOS inhibitor aminoguanidine. At 1 h after LPS administration, bladder NO generation, endothelial NOS expression, and EFS-evoked detrusor contractions were effectively increased, whereas anti-IL-6 antibody could not reverse these LPS-induced responses. These results indicate that IL-6 may play an important role in the iNOS/NO-triggered PKC-activated contractile response in urinary bladder during E. coli or LPS-induced inflammation.
Weng
Te I
TI
Department of Forensic Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Wu
Hsiao Yi
HY
Lin
Pei Ying
PY
Liu
Shing Hwa
SH
D000818:Animals; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000473:pathology*; D005260:Female; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D009119:Muscle Contraction; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology*
D015850:Interleukin-6; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II