This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, B. Articles by Cohen, R. A. Search for Related Content PubMed PubMed Citation Articles by Jiang, B. Articles by Cohen, R. A. Related Collections Cell signalling/signal transduction Growth factors/cytokines Mechanism of atherosclerosis/growth factors

(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

This article has been cited by other articles:

				P. R. Nagareddy, H. Soliman, G. Lin, P. S. Rajput, U. Kumar, J. H. McNeill, and K. M. MacLeod Selective Inhibition of Protein Kinase C {beta}2 Attenuates Inducible Nitric Oxide Synthase-Mediated Cardiovascular Abnormalities in Streptozotocin-Induced Diabetic Rats Diabetes, October 1, 2009; 58(10): 2355 - 2364. [Abstract] [Full Text] [PDF]

				W. Hu, F. Li, S. Mahavadi, and K. S. Murthy Upregulation of RGS4 expression by IL-1{beta} in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3{beta} pathway Am J Physiol Cell Physiol, June 1, 2009; 296(6): C1310 - C1320. [Abstract] [Full Text] [PDF]

				A. Virdis, R. Colucci, D. Versari, N. Ghisu, M. Fornai, L. Antonioli, E. Duranti, E. Daghini, C. Giannarelli, C. Blandizzi, et al. Atorvastatin Prevents Endothelial Dysfunction in Mesenteric Arteries From Spontaneously Hypertensive Rats: Role of Cyclooxygenase 2-Derived Contracting Prostanoids Hypertension, June 1, 2009; 53(6): 1008 - 1016. [Abstract] [Full Text] [PDF]

				M. Minami, K. Shimizu, Y. Okamoto, E. Folco, M.-L. Ilasaca, M. W. Feinberg, M. Aikawa, and P. Libby Prostaglandin E Receptor Type 4-associated Protein Interacts Directly with NF-{kappa}B1 and Attenuates Macrophage Activation J. Biol. Chem., April 11, 2008; 283(15): 9692 - 9703. [Abstract] [Full Text] [PDF]

				T. Machida, Y. Hamaya, S. Izumi, Y. Hamaya, K. Iizuka, Y. Igarashi, M. Minami, R. Levi, and M. Hirafuji Sphingosine 1-Phosphate Inhibits Nitric Oxide Production Induced by Interleukin-1{beta} in Rat Vascular Smooth Muscle Cells J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 200 - 209. [Abstract] [Full Text] [PDF]

				A. Kennedy, S. Chung, K. LaPoint, O. Fabiyi, and M. K. McIntosh Trans-10, Cis-12 Conjugated Linoleic Acid Antagonizes Ligand-Dependent PPAR{gamma} Activity in Primary Cultures of Human Adipocytes J. Nutr., March 1, 2008; 138(3): 455 - 461. [Abstract] [Full Text] [PDF]

				A. Tanimoto, K.-Y. Wang, Y. Murata, S. Kimura, M. Nomaguchi, S. Nakata, M. Tsutsui, and Y. Sasaguri Histamine Upregulates the Expression of Inducible Nitric Oxide Synthase in Human Intimal Smooth Muscle Cells via Histamine H1 Receptor and NF-{kappa}B Signaling Pathway Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1556 - 1561. [Abstract] [Full Text] [PDF]

				R. Zhande and A. Karsan Erythropoietin promotes survival of primary human endothelial cells through PI3K-dependent, NF-{kappa}B-independent upregulation of Bcl-xL Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2467 - H2474. [Abstract] [Full Text] [PDF]

				J.-S. Park, M.-S. Woo, D.-H. Kim, J.-W. Hyun, W.-K. Kim, J.-C. Lee, and H.-S. Kim Anti-Inflammatory Mechanisms of Isoflavone Metabolites in Lipopolysaccharide-Stimulated Microglial Cells J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1237 - 1245. [Abstract] [Full Text] [PDF]

				S. Xu, H. Bayat, X. Hou, and B. Jiang Ribosomal S6 kinase-1 modulates interleukin-1beta-induced persistent activation of NF-{kappa}B through phosphorylation of I{kappa}Bbeta Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1336 - C1345. [Abstract] [Full Text] [PDF]

				X. Yang, V. Murthy, K. Schultz, J. B. Tatro, K. A. Fitzgerald, and D. Beasley Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2334 - H2343. [Abstract] [Full Text] [PDF]

				T. Coll, M. Jove, R. Rodriguez-Calvo, E. Eyre, X. Palomer, R. M. Sanchez, M. Merlos, J. C. Laguna, and M. Vazquez-Carrera Palmitate-Mediated Downregulation of Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator 1{alpha} in Skeletal Muscle Cells Involves MEK1/2 and Nuclear Factor-{kappa}B Activation. Diabetes, October 1, 2006; 55(10): 2779 - 2787. [Abstract] [Full Text] [PDF]

				W. G. Aschenbach, R. C. Ho, K. Sakamoto, N. Fujii, Y. Li, Y.-B. Kim, M. F. Hirshman, and L. J. Goodyear Regulation of Dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E152 - E158. [Abstract] [Full Text] [PDF]

				R. Ginnan, B. J. Guikema, H. A. Singer, and D. Jourd'heuil PKC-{delta} mediates activation of ERK1/2 and induction of iNOS by IL-1beta in vascular smooth muscle cells Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1583 - C1591. [Abstract] [Full Text] [PDF]

				S. Chung, J. M. Brown, J. N. Provo, R. Hopkins, and M. K. McIntosh Conjugated Linoleic Acid Promotes Human Adipocyte Insulin Resistance through NF{kappa}B-dependent Cytokine Production J. Biol. Chem., November 18, 2005; 280(46): 38445 - 38456. [Abstract] [Full Text] [PDF]

				P. F. Gomez, M. H. Pillinger, M. Attur, N. Marjanovic, M. Dave, J. Park, C. O. Bingham III, H. Al-Mussawir, and S. B. Abramson Resolution of Inflammation: Prostaglandin E2 Dissociates Nuclear Trafficking of Individual NF-{kappa}B Subunits (p65, p50) in Stimulated Rheumatoid Synovial Fibroblasts J. Immunol., November 15, 2005; 175(10): 6924 - 6930. [Abstract] [Full Text] [PDF]

				B. Jiang, S. Xu, X. Hou, D. R. Pimentel, and R. A. Cohen Angiotensin II Differentially Regulates Interleukin-1-{beta}-inducible NO Synthase (iNOS) and Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression: ROLE OF p38 MAPK J. Biol. Chem., May 7, 2004; 279(19): 20363 - 20368. [Abstract] [Full Text] [PDF]

				B. Jiang, S. Xu, X. Hou, D. R. Pimentel, P. Brecher, and R. A. Cohen Temporal Control of NF-{kappa}B Activation by ERK Differentially Regulates Interleukin-1{beta}-induced Gene Expression J. Biol. Chem., January 9, 2004; 279(2): 1323 - 1329. [Abstract] [Full Text] [PDF]

				J. F. Kurland, D. W. Voehringer, and R. E. Meyn The MEK/ERK Pathway Acts Upstream of NF{kappa}B1 (p50) Homodimer Activity and Bcl-2 Expression in a Murine B-Cell Lymphoma Cell Line: MEK INHIBITION RESTORES RADIATION-INDUCED APOPTOSIS J. Biol. Chem., August 22, 2003; 278(34): 32465 - 32470. [Abstract] [Full Text] [PDF]

				B. Jiang, S. Xu, P. Brecher, and R. A. Cohen Growth Factors Enhance Interleukin-1{beta}-Induced Persistent Activation of Nuclear Factor-{kappa}B in Rat Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1811 - 1816. [Abstract] [Full Text] [PDF]