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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1915.)
© 2001 American Heart Association, Inc.

Vascular Biology

Persistent Activation of Nuclear Factor-B by Interleukin-1ß and Subsequent Inducible NO Synthase Expression Requires Extracellular Signal-Regulated Kinase

Bingbing Jiang; Peter Brecher; Richard A. Cohen

From the Whitaker Cardiovascular Institute, Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Bingbing Jiang, PhD, Whitaker Cardiovascular Institute, Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, 650 Albany St, X704, Boston, MA 02118. E-mail bjiang{at}bu.edu

The role of extracellular signal-regulated kinase (ERK) was studied in the signaling pathway by which interleukin-1ß (IL-1ß) increases the expression of inducible NO synthase (iNOS) in rat vascular smooth muscle cells. IL-1ß induced a rapid and transient activation of nuclear factor-B (NF-B), followed by a prolonged activation of NF-B that was required to induce iNOS expression. Either PD98059 or U0126, selective inhibitors of ERK activation, did not influence IL-1ß-induced early activation but effectively reduced the prolonged activation of NF-B and significantly reduced IL-1ß induction of iNOS. Transfection with antisense, but not sense, phosphorothioate-modified oligodeoxynucleotides directed toward ERK also reduced IL-1ß-induced prolonged NF-B activation and iNOS expression. IBß, but not IB degradation, induced by IL-1ß was markedly attenuated when ERK activation was inhibited and could be partially responsible for the persistent NF-B activation. These data suggest that ERK activity is required for persistent NF-B activation by IL-1ß that is necessary for iNOS gene expression.

Key Words: extracellular signal-regulated kinase • interleukin-1ß • NO synthase • nuclear factor-B • vascular smooth muscle cells

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