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(Hypertension. 1999;34:574-579.)
© 1999 American Heart Association, Inc.

Scientific Contributions

N-Acetyl-L-Cysteine Enhances Interleukin-1ß–Induced Nitric Oxide Synthase Expression

Bingbing Jiang; Michael Haverty; Peter Brecher

From the Department of Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, Mass.

Correspondence to Peter Brecher, PhD, Department of Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118. E-mail pbrecher{at}acs.bu.edu

Abstract—The effect of N-acetyl-L-cysteine on interleukin-1ß–induced nitric oxide synthase expression was studied in rat vascular smooth muscle cells to determine if the reduction/oxidation state would modulate cytokine-induced changes. Interleukin-1ß induced the production of nitrite, a stable metabolite of nitric oxide in a time- and dose-dependent manner. Cytokine-induced nitrite production was enhanced by the addition of N-acetyl-L-cysteine in a dose-dependent manner, with a >50% increase produced by the addition of 1 mmol/L N-acetyl-L-cysteine. There was no influence on nitrite production when the cells were treated with N-acetyl-L-cysteine alone. Northern and Western blot analyses revealed that the upregulation of interleukin-1ß–induced nitric oxide production by N-acetyl-L-cysteine resulted from an enhanced expression of inducible nitric oxide synthase. Interferon- or tumor necrosis factor- when used alone had no influence on nitrite production in the absence or presence of N-acetyl-L-cysteine. Nitrite accumulation was higher by the cells treated with interleukin-1ß combined with either interferon- or tumor necrosis factor- compared with those treated with interleukin-1ß alone. N-Acetyl-L-cysteine upregulated nitrite production and inducible nitric oxide synthase expression induced by combination treatment with interleukin-1ß and either interferon- or tumor necrosis factor-. However, N-acetyl-L-cysteine had no significant influence in cytokine-induced activation of nuclear factor-B or signal transducer and activator of transciption-1, as assessed by electrophoretic mobility shift assays. These results demonstrate that N-acetyl-L-cysteine possibly acted as a thiol-containing reducing agent and facilitated the expression of inducible nitric oxide synthase in rat vascular smooth muscle cells by cytokines through a mechanism that is independent of nuclear factor-B or signal transducer and activator of transciption-1.

Key Words: acetylcysteine • cytokines • nitric oxide • RNA • interleukins • muscle, smooth, vascular

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