Open AccessPersistent Activation of Nuclear Factor-κB by Interleukin-1β and Subsequent Inducible NO Synthase Expression Requires Extracellular Signal-Regulated Kinase
Author(s) -
Bingbing Jiang,
Peter Brecher,
Richard A. Cohen
Publication year - 2001
Publication title -
arteriosclerosis, thrombosis, and vascular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.007
H-Index - 270
eISSN - 1524-4636
pISSN - 1079-5642
DOI - 10.1161/hq1201.099424
Subject(s) - mapk/erk pathway , extracellular , kinase , signal transduction , mitogen activated protein kinase 3 , microbiology and biotechnology , nfkb1 , transfection , biology , nf κb , mitogen activated protein kinase , chemistry , transcription factor , biochemistry , gene
Abstract —The role of extracellular signal-regulated kinase (ERK) was studied in the signaling pathway by which interleukin-1β (IL-1β) increases the expression of inducible NO synthase (iNOS) in rat vascular smooth muscle cells. IL-1β induced a rapid and transient activation of nuclear factor-κB (NF-κB), followed by a prolonged activation of NF-κB that was required to induce iNOS expression. Either PD98059 or U0126, selective inhibitors of ERK activation, did not influence IL-1β-induced early activation but effectively reduced the prolonged activation of NF-κB and significantly reduced IL-1β induction of iNOS. Transfection with antisense, but not sense, phosphorothioate-modified oligodeoxynucleotides directed toward ERK also reduced IL-1β-induced prolonged NF-κB activation and iNOS expression. IκBβ, but not IκBα degradation, induced by IL-1β was markedly attenuated when ERK activation was inhibited and could be partially responsible for the persistent NF-κB activation. These data suggest that ERK activity is required for persistent NF-κB activation by IL-1β that is necessary for iNOS gene expression.