Interleukin-1β inhibits PDGF-BB−induced migration by cooperating with PDGF-BB to induce cyclooxygenase-2 expression in baboon aortic smooth muscle cells
| Autor: | Michael J. Englesbe, Günter Daum, Alexander W. Clowes, Jessie Deou, Brenda D Bourns |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_treatment
p38 mitogen-activated protein kinases Blotting Western Becaplermin 030204 cardiovascular system & hematology p38 Mitogen-Activated Protein Kinases Muscle Smooth Vascular 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Animals Humans Protein kinase A Aorta 030304 developmental biology Platelet-Derived Growth Factor 0303 health sciences biology business.industry Growth factor Interleukin Cell Migration Inhibition Proto-Oncogene Proteins c-sis Molecular biology Recombinant Proteins Cytokine Prostaglandin-Endoperoxide Synthases Immunology biology.protein Surgery Cyclooxygenase Mitogen-Activated Protein Kinases Tunica Intima Cardiology and Cardiovascular Medicine business Platelet-derived growth factor receptor Interleukin-1 Papio |
| Zdroj: | Journal of Vascular Surgery. (5):1091-1096 |
| ISSN: | 0741-5214 |
| DOI: | 10.1016/j.jvs.2004.01.041 |
| Popis: | ObjectiveSmooth muscle cell (SMC) migration from the media into the intima is pivotal for intimal formation after vascular injury. Platelet-derived growth factor (PDGF)-BB is a potent chemoattractant for SMCs in vitro and in vivo. We investigated whether interleukin (IL)–1β affects migration in response to PDGF-BB. Our data suggest that IL-1β is inhibitory and that this effect is mediated by cyclooxygenase (COX)–2. We further addressed the role of the mitogen-activated protein kinase p38, which is activated by PDGF-BB and by IL-1β.MethodsBaboon aortic SMCs were prepared with the explant method. Migration was measured in a Boyden chamber assay through filters coated with monomeric collagen. COX2 expression and phosphorylation of p38 MAPK were analyzed by Western blotting.ResultsPDGF-BB (10 ng/mL) stimulates migration 3.8-fold, and IL-1β (0.1 ng/mL) reduces this response by 40%. The inhibitory effect of IL-1β is abolished by the COX inhibitor, indomethacin (10 μmol/L), the specific COX2 inhibitor, NS398 (10 μmol/L), and the p38 MAPK inhibitor SB203580 (3 μmol/L). We found that IL-1β and PDGF-BB synergize to stimulate COX2 expression. We further demonstrated that p38 MAPK is activated by IL-1β and PDGF with different kinetics and that p38 MAPK is required for maximal COX2 expression in response to IL-1β plus PDGF-BB.ConclusionIL-1β inhibits PDGF-BB–induced migration by cooperating with PDGF-BB to induce COX2 through activation of p38 MAPK. Whether this effect of IL-1β modulates intimal growth after vascular injury remains to be elucidated.AbstractClinical relevanceRestenosis is the cause of the unacceptably high failure rate of surgical interventions (such as vein grafts, stents, and angioplasty) to restore blood flow in occluded vessels. It is clear that inflammatory processes are critical for the development and progression of atherosclerotic lesions, and there is increasing evidence that inflammation also contributes to restenosis. Recent observations that IL-1 receptors, agonists, and antagonists are expressed upon arterial injury in various animal models strongly indicate a role for IL-1 in restenosis. This study investigates the effects of IL-1 on SMC migration, which is critical for the formation of an occluding intima. Our results suggest that IL-1 may limit the accumulation of intimal cells after injury by blocking SMC migration in a mechanism that depends on expression of cyclooxygenase-2. |
| Databáze: | OpenAIRE |
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