Nitric oxide synthase 1 and cyclooxygenase-2 enzymes are targets of muscarinic activation in normal and inflamen NIH3T3 cells

ESPAÑOL, ALEJANDRO JAVIER; GOREN NORA; RIBEIRO MARÍA; SALES MARÍA ELENA

INFLAMMATION RESEARCH

BIRKHAUSER VERLAG AG

Año: 2009 vol. 59 p. 227 - 238

1023-3830

Inflammation, a highly regulated response to infection and injury, has evolved as a beneficial component of the physiological defense system of the host organism. Lypopolysaccharide (LPS) is a major constituent of the outer membrane of Gram-negative bacteria and the combination of this endotoxin with inflammatory cytokines (i.e. interferon gamma) acts synergistically to up-regulate pro-inflammatory genes expression. Here we investigate the action of the muscarinic agonist carbachol (CARB) on the expression and function of nitric oxide synthase (NOS) and cyclooxygenase (COX) in normal murine fibroblasts NIH3T3, that express muscarinic acetylcholine receptors, treated with LPS plus interferon gamma (IFNg). We observed that treated cells up-regulate NOS1 and COX-2 expression via nuclear factor kappa B (NF-kB) activation. CARB exerts a stimulatory action on nitric oxide (NO) and prostaglandin E2 (PGE2) synthesis, revealing a positive regulatory effect of COX-2 products on NO production and a negative feed back of the latter mediator, on COX-2 activity. We also observed that CARB synergizes LPS plus IFNg action on NF-kB pathway acting as a pro-inflammatory stimulus on NIH3T3 cells