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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2002.1
- 수록면
- 451 - 461 (11page)
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Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, are widely used for primary and secondary prevention atherosclerosis is multistep processes where trans-endothelial migration of various leukocytes includ-ing monocytes is a crucial step. Interferon-γ (IFN-γ) contributes in this process by activating macro-phages and T-lymphocytes, and by inducing adhe-sion molecules in vascular endothelial and smooth muscle cells. In this study we investigated the expresion of intercellular cell adhesion mole-cule-1 (ICAM-1) in transformed endothelial cell line ECV304 cells as influenced by lovastatin, tumor necrosis factor-α (TNF-α) and IFN-γ. Results show that lovastatin suppresses expression of ICAM-1 by inhibiting the IFN-γ-induced extracellular signal- regulated kinase (ERK) p44/p42-STAT1 signaling pathway. In cells treated with lovastatin and IFN-γ, ICAM-1 was expressed at a lower level than in cells treated with IFN-γ alone. However, lovastatin does not reduce TNF-α induced expression of ICAM-1. A similar result was observed in cells N-γ. Cis-acting DNA sequence elements were identified in the 5'-flanking region of the ICAM-1 promoter that mediate inhibition by lovastatin; these se-quences map to the IFN-γ activated site which also binds the STAT1 homodimer. However, lovastatin did not inhibit IFN-γ-mediated induction of the Y701 phosphorylated form of STAT1. But lovasta-tin does inhibit the IFN-γ-mediated phosphoryla-tion of ERK1/ERK2 (T202/Y204) and S727 phos-phorylation of STAT1. TNF-αphosphorylation of ERK1/ERK2 and S727 in ECV304 and smooth muscle cels. The results provide the evidences that statins may have beneficial effects by inhibiting IFN-γ action in atherosclerotic pro-cess
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