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Vol. 63, Issue 3, 671-677, March 2003

Selective Inhibitors of Cyclooxygenase-2 Delay the Activation of Nuclear Factor kappa B and Attenuate the Expression of Inflammatory Genes in Murine Macrophages Treated with Lipopolysaccharide

Nuria A. Callejas, Amalia Fernández-Martínez, Antonio Castrillo, Lisardo Boscá, and Paloma Martín-Sanz

Instituto de Bioquímica, Centro Mixto Consejo Superior de Investigaciones Cientificas-Universidad Complutense de Madrid, Facultad de Farmacia, Universidad Complutense, Madrid, Spain

The effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on inflammatory signaling has been investigated in elicited murine peritoneal macrophages. Macrophages treated with 10 µM rofecoxib exhibited an important inhibition in the early activation of nuclear factor kappa B (NF-kappa B) and the mitogen-activated protein kinase p38, the extracellular-regulated kinase p44, and the c-Jun N-terminal kinase. Moreover, this drug decreased the protein levels of nitric-oxide synthase-2 and cyclooxygenase-2 in lipopolysaccharide (LPS)-treated macrophages. Rofecoxib delayed and attenuated NF-kappa B activation, which impaired significantly the expression of kappa B-dependent genes. This drug and related coxibs did not affect cell viability and protected against LPS-induced apoptosis through the impairment of the inflammatory response. These data show an additional anti-inflammatory mechanism of selective cyclooxygenase-2 inhibitors through the attenuation of macrophage activation.

Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics