Interleukin-1 beta induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells.
Increased expression of cell adhesion molecules is an important pathological event during the development of atherosclerosis. The smooth muscle cell (SMC) is one of the cell types present in the atherosclerotic lesion. To evaluate the regulation of adhesion molecules in human vascular SMCs and its possible role, we studied the expression of adhesion molecules in SMCs stimulated with interleukin 1-beta (IL-1 beta), a pleiotropic cytokine that is involved in the pathological development of vascular diseases including atherosclerosis and restenosis. Our data demonstrated that IL-1 beta markedly induced the adhesiveness of human vascular SMCs for monocytes and neutrophils in a concentration (10 pM - 10 nM)- and time (0.5-24 h)-dependent manner. The maximal induced adhesion by IL-1 beta (1 nM) was reached at 4 h, with 4.6-fold and 3.3-fold for monocytes and neutrophils, respectively. This induction was dose-dependently inhibited by the IL-1 receptor antagonist (IL-1 ra). The IL-1 beta-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin 1 (ELAM-1) on SMCs was examined by reverse transcription/polymerase chain reaction (RT/PCR). Unstimulated, serum-deprived SMCs expressed a low or undetectable level of mRNA for these adhesion molecules. The expression of ICAM-1 and VCAM-1 but not ELAM-1 mRNA was significantly induced with IL-1 beta in a concentration (1 fM - 1 nM)- and time (0.5 - 24 h)-dependent manner. The maximal increase in ICAM-1 and VCAM-1 mRNAs was reached at 4 h after IL-1 beta stimulation. The IL-1 beta-induced adhesion of SMCs for monocytes was partially inhibited by monoclonal anti-human ICAM-1 and anti-human VCAM-1 antibody, but not by anti-human ELAM-1 antibody. Pretreatment of monocytes with anti-human integrin beta 2 antibody significantly reduced the adhesion of monocytes to IL-1 beta-stimulated SMCs. These results suggest that IL-1 beta is a potent inducer for ICAM-1 and VCAM-1 expression in human vascular SMC, and could play a role in the pathogenesis of atherosclerosis by recruitment and retention of inflammatory cells such as monocytes and neutrophils in the lesions.
Wang
X
X
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Feuerstein
G Z
GZ
Gu
J L
JL
Lysko
P G
PG
Yue
T L
TL
D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D019040:E-Selectin; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1