Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation.
Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with epithelial sodium channel activation and tumor invasion suppression activities. We identified the bladder as an expression site of prostasin. In the mouse, prostasin mRNA expression was detected by reverse transcription and real-time polymerase chain reaction in the bladder, and the prostasin protein was localized by immunohistochemistry in the urothelial cells. In mice injected intraperitoneally with bacterial lipopolysaccharide (LPS), bladder prostasin mRNA expression was downregulated, whereas the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-gamma (IFN-gamma), TNF-alpha, IL-1beta, and IL-6 was upregulated. Viral promoter-driven expression of the human prostasin homolog in the bladder of transgenic mice attenuated the LPS induction of iNOS but did not abolish the induction. LPS induction of COX-2, TNF-alpha, IL-1beta, and IL-6 expression, however, was not reduced by prostasin transgene expression. Liposome-mediated delivery of prostasin-expressing plasmid into mouse bladder produced similar attenuation effects on LPS-induced iNOS expression, while not affecting COX-2 or cytokine induction. Mice receiving plasmid expressing a catalytic mutant prostasin did not manifest the iNOS induction attenuation phenotype. We propose a proteolytic mechanism for prostasin to intercept cytokine signaling during LPS-induced bladder inflammation.
Chen
Li-Mei
LM
Department of Molecular Biology and Microbiology, University of Central Florida, 4000 Central Florida Boulevard, Orlando, FL 32816-2364, USA.
Wang
Cindy
C
Chen
Mengqian
M
Marcello
Matthew R
MR
Chao
Julie
J
Chao
Lee
L
Chai
Karl X
KX
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000503:physiopathology*; D019459:Urothelium / Q000378:metabolism; D000099271:Prostasin
D051546:Cyclooxygenase 2; D007371:Interferon-gamma; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D012697:Serine Endopeptidases; D014409:Tumor Necrosis Factor-alpha; D000099271:Prostasin; C496317:Nos2 protein, mouse