Selective inhibitors of cyclooxygenase-2 delay the activation of nuclear factor κB and attenuate the expression of inflammatory genes in murine macrophages treated with lipopolysaccharide

The effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on inflammatory signaling has been investigated in elicited murine peritoneal macrophages. Macrophages treated with 10 muM rofecoxib exhibited an important inhibition in the early activation of nuclear factor kappaB (NF-kappaB) 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 macro-phages. Rofecoxib delayed and attenuated NF-kappaB activation, which impaired significantly the expression of kappaB-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.