Interleukin-1 and transforming growth factor-alpha: synergistic stimulation of metalloproteinases, PGE2, and proliferation in human fibroblasts.
Interleukin-1 and transforming growth factor-alpha: synergistic stimulation of metalloproteinases, PGE2, and proliferation in human fibroblasts.
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Interleukin-1 和转化生长因子-α：金属蛋白酶、PGE2 和人成纤维细胞增殖的协同刺激。
DOI：
10.1006/excr.1994.1025
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发表时间：
1994
影响因子：
3.7
通讯作者：
Amento,EP
中科院分区：
文献类型：
--
作者：
Unemori,EN;Ehsani,N;Wang,M;Lee,S;McGuire,J;Amento,EP
伤口愈合和其他炎症过程由细胞、细胞外基质和各种细胞类型的分泌产物之间的一系列复杂的相互作用驱动。细胞因子，如白细胞介素-1和转化生长因子-α，存在于伤口部位，并有助于这些部位的促炎环境。在本研究中，我们已经调查了这些细胞因子的影响，单独和一致，对成纤维细胞表达的基质金属蛋白酶，这有助于细胞外基质重塑，前列腺素E2，改变血管张力和渗透性。金属蛋白酶，前胶原酶（基质金属蛋白酶-1）和前基质溶解素（基质金属蛋白酶-3），是由皮肤成纤维细胞暴露于白细胞介素-1诱导的，不受转化生长因子-α刺激，但由细胞因子组合协同诱导。92-kDa IV型前胶原酶（基质金属蛋白酶-9，胶原酶B）也以协同方式被刺激。前列腺素E2在类风湿性滑膜成纤维细胞中由白细胞介素-1 β诱导，不受转化生长因子-α的影响，并通过两种细胞因子的组合协同释放。成纤维细胞增殖也是正常伤口愈合的组成部分，也通过两种细胞因子的协同作用协同刺激。这些结果表明，白细胞介素-1 β和转化生长因子-α协同作用，在成纤维细胞中引发许多与正常伤口愈合和慢性炎症相关的表型应答。
Wound healing and other inflammatory processes are driven by a complex series of interactions among cells, the extracellular matrix, and secreted products of various cell types. Cytokines, such as interleukin-1 and transforming growth factor-α, are present at wound sites and contribute to the proinflammatory milieu of these sites. In the present study, we have investigated the effect of these cytokines, individually and in concert, on fibroblast expression of matrix metalloproteinases, which contribute to extracellular matrix remodeling, and of prostaglandin E2, which alters vascular tone and permeability. The metalloproteinases, procollagenase (matrix metalloproteinase-1) and prostromelysin (matrix metalloproteinase-3), are induced by exposure of dermal fibroblasts to interleukin-1, not stimulated by transforming growth factor-α, but are synergistically induced by the combination of cytokines. The 92-kDa type IV procollagenase (matrix metalloproteinase-9, progelatinase B), is also stimulated in synergistic fashion. Prostaglandin E2is induced in rheumatoid synovial fibroblasts by interleukin-1β, not altered by transforming growth factor-α, and is synergistically released by the combination of the two cytokines. Fibroblast proliferation, which is also a component of normal wound healing, is also synergistically stimulated by the action of the two cytokines in concert. These results indicate that interleukin-1β and transforming growth factor-α, synergize to elicit a number of phenotypic responses in fibroblasts which are relevant to normal wound healing and chronic inflammation.