N -Acetyl- l -Cysteine Potentiates Interleukin-1β Induction of Nitric Oxide Synthase

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Abstract
—We have reported previously that N-acetyl-l-cysteine facilitated interleukin-1β–induced nitric oxide synthase (iNOS) expression in rat vascular smooth muscle cells. The present study compares the effect of N-acetyl-l-cysteine with other antioxidants and tested the possibility that N-acetyl-l-cysteine potentiates iNOS induction by a mechanism involving activation of p44/42 mitogen-activated protein kinases (MAPKs). The effect of N-acetyl-l-cysteine on potentiating interleukin-1β–induced nitrite production and iNOS expression was mimicked either by the enantiomers, l-cysteine and d-cysteine, or by a non–thiol-containing antioxidant, l-ascorbic acid. Interleukin-1β activated p44/42 MAPK, and this activation was enhanced in the presence of N-acetyl-l-cysteine. Inhibition of p44/42 MAPK phosphorylation by the selective inhibitor PD98059 clearly inhibited iNOS expression induced by interleukin-1β either in the absence or in the presence of N-acetyl-l-cysteine. These observations, combined with previous...

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