Nitric oxide and superoxide in rat mesangial cells: modulation by C-reactive protein.
BACKGROUND
C-reactive protein (CRP) has been linked to cardiovascular and renal disease. We evaluated the effects of CRP on the production of nitric oxide (NO) and superoxide by rat mesangial cells (RMC) and the impact on cell function.


RESULTS
RMC were incubated with cytokines (IFN-gamma, IL-1beta, and LPS) and CRP (10-100 microg/ml) for 24-72 h. Exposure to CRP resulted in a time- and dose-dependent reduction in NO accumulation (p<0.05). Although inducible nitric oxide synthase (iNOS) protein expression was unaltered after 48 h, CRP stimulated expression of HSP90. Steady state abundance of iNOS mRNA increased nearly threefold after a 24-h exposure to CRP. Incubation with 100 microg/ml CRP for 60-120 min resulted in a 272% increase in superoxide production that was prevented by diphenyleneiodium chloride but not L-NAME (p<0.0001).


CONCLUSIONS
CRP enhances superoxide release in RMC, which in turn inactivates NO and reduces net production. The functional relevance of these CRP-induced changes is supported by increased expression of HSP90 in RMC exposed to the mediator. These findings suggest that systemic inflammation, which contributes to the pathogenesis of atherosclerosis, may play a role in the progression of kidney disease.
Department of Pediatrics (Division of Nephrology), Schneider Children's Hospital, Albert Einstein College of Medicine, New Hyde Park, NY 11040-1432, USA. trachtma@lij.edu
Howard
H
Trachtman
Stephen
S
Futterweit
Christopher
C
Arzberger
Jessica
J
Bod
Judah
J
Goldschmiedt
Haddassah
H
Gorman
Krishna
K
Reddy
Nicholas
N
Franki
Pravin C
PC
Singhal
D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D013481:Superoxides; D009569:Nitric Oxide; D007371:Interferon-gamma; D002097:C-Reactive Protein; D052247:Nitric Oxide Synthase Type II