CYTOKINES AND GROWTH-FACTORS POSITIVELY AND NEGATIVELY REGULATE INTERSTITIAL COLLAGEN GENE-EXPRESSION IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS
CYTOKINES AND GROWTH-FACTORS POSITIVELY AND NEGATIVELY REGULATE INTERSTITIAL COLLAGEN GENE-EXPRESSION IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS
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DOI：
10.1161/01.atv.11.5.1223
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发表时间：
1991-09-01
期刊：
影响因子：
--
通讯作者：
LIBBY, P
中科院分区：
文献类型：
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作者：
AMENTO, EP;EHSANI, N;LIBBY, P
人类动脉粥样硬化积累细胞外基质蛋白，如I型和III型胶原蛋白。 我们测试了人类动脉粥样硬化斑块中发现的细胞产生的细胞因子或生长因子是否会改变血管平滑肌细胞（VSMC）中胶原基因的表达，VSMC产生血管基质。 白细胞介素-1（IL-1，1 - 10 ng/ml）适度增加胶原蛋白I和III的合成（通过掺入特定电泳条带的氚化脯氨酸测量），而转化生长因子-β（TGF-β）或血小板衍生生长因子（PDGF）显著刺激这些间质胶原蛋白的产生。 干扰素-γ（IFN-γ），一种在动脉粥样硬化中发现的活化T细胞的产物，选择性地改变几种VSMC功能。 例如，这种细胞因子减少VSMC的生长，降低α-肌动蛋白基因表达，并诱导VSMC表达II类组织相容性抗原。 我们在这里报告，IFN-γ也抑制基础以及IL-1-，PDGF-，或TGF-β-stimualated胶原蛋白I和III的人VSMCs的合成。 TGF-β是此处研究的最有效的胶原合成刺激剂，使VSMCs中的胶原III mRNA水平升高4.8倍（通过北方印迹光密度测定法测定），而暴露于TGF-β和IFN-γ均使该mRNA水平降低至基础水平的0.5倍。 因此，局部产生的细胞因子和生长因子可能通过刺激或抑制VSMCs间质胶原mRNA和蛋白的表达来改变动脉粥样硬化形成过程中的基质积累。
Human atheromas accumulate extracellular matrix proteins such as collagen types I and III. We tested whether cytokines or growth factors produced by cells found in human atherosclerotic plaques alter collagen gene expression in vascular smooth muscle cells (VSMCs), which produce the blood vessel matrix. Interleukin-1 (IL-1, 1-10 ng/ml) modestly increased the synthesis of collagens I and III (measured by tritiated proline incorporation into specific electrophoretic bands), whereas transforming growth factor-beta (TGF-beta) or platelet-derived growth factor (PDGF) markedly stimulated production of these interstitial collagens. Interferon gamma (IFN-gamma), a product of activated T cells found in atheromas, selectively alters several VSMC functions. For example, this cytokine reduces growth of VSMCs, decreases alpha-actin gene expression, and induces VSMC expression of class II histocompatibility antigens. We report here that IFN-gamma also inhibits basal as well as IL-1-, PDGF-, or TGF-beta-stimualted collagen I and III synthesis by human VSMCs. TGF-beta, the most potent stimulator of collagen synthesis studied here, raised the level of collagen III mRNA in VSMCs 4.8-fold (determined by densitometry of Northern blots), whereas exposure to both TGF-beta and IFN-gamma reduced this mRNA to 0.5 of basal level. Locally produced cytokines and growth factors may thus modify matrix accumulation during atherogenesis by stimulating or suppressing expression of interstitial collagen mRNA and protein by VSMCs.