HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H2927    most recent 00700.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Schultz, K. Articles by Beasley, D. Search for Related Content PubMed PubMed Citation Articles by Schultz, K. Articles by Beasley, D.

Endogenous interleukin-1 promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells

¹Molecular Cardiology Research Institute and ²Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts

Submitted 30 June 2006 ; accepted in final form 5 February 2007

During vascular disease and following injury, vascular smooth muscle cells (VSMC) proliferate and produce inflammation-promoting cytokines and chemokines. Similar phenotypic changes can be elicited in vitro by activation of Toll-like receptors (TLR) within VSMC. TLR-activated VSMC also produce IL-1, but it is unknown whether endogenous IL-1 stimulates VSMC in an autocrine manner. Here we tested the hypothesis that endogenous IL-1 contributes to TLR-induced proliferation and chemokine release in human VSMC by using RNA interference to knock down IL-1 expression. Knockdown of IL-1 abolished TLR-induced proliferation and suppressed TLR4-induced release of monocyte chemoattractant protein-1 (MCP-1) by VSMC, indicating that endogenous IL-1 plays a crucial role in both responses. Serum, PDGF, FGF-2, and EGF each increased cellular IL-1 concentrations, and IL-1 knockdown inhibited serum- and PDGF-induced DNA synthesis, further indicating that endogenous IL-1 also contributed to VSMC responses to growth factors. IL-1 receptor antagonist, a competitive inhibitor of IL-1 receptor I (IL-1RI), also attenuated TLR-induced proliferation and both basal and TLR-induced MCP-1 expression, indicating at least a partial role of the IL-1RI in mediating these responses. The results support the hypothesis that autocrine actions of endogenous IL-1, mediated at least in part via IL-1RI signaling, contribute to a proproliferative and proinflammatory phenotypic shift in TLR-activated human VSMC, which might play a pathogenic role in vascular disorders.

monocyte chemoattractant protein-1; cell proliferation; type I interleukin-1 receptor

This article has been cited by other articles:

				X. Wu, Q. Zhou, L. Huang, A. Sun, K. Wang, Y. Zou, and J. Ge Ageing-exaggerated proliferation of vascular smooth muscle cells is related to attenuation of Jagged1 expression in endothelial cells Cardiovasc Res, March 1, 2008; 77(4): 800 - 808. [Abstract] [Full Text] [PDF]