Interleukin-1-induced growth factor expression in postmitotic and resting fibroblasts
Interleukin-1-induced growth factor expression in postmitotic and resting fibroblasts
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DOI：
10.1111/1523-1747.ep12331158
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发表时间：
1996-12-01
影响因子：
6.5
通讯作者：
Fusenig, NE
中科院分区：
文献类型：
--
作者：
MaasSzabowski, N;Fusenig, NE
皮肤中的组织稳态由上皮-间充质相互作用调节，主要通过扩散因子起作用。为了研究潜在的调节机制，已经建立了体外系统来模拟皮肤中的体内情况。在共培养物中，角质形成细胞在塑料上或在含有成纤维细胞的胶原凝胶的顶部上与经照射的成纤维细胞相邻地生长，从而形成三维器官型结构。角质形成细胞生长部分地由成纤维细胞产生的因子支持，所述因子由角质形成细胞介体如白细胞介素-1（IL-1）诱导。为了更好地理解这种细胞相互作用及其通过成纤维细胞增殖和细胞外基质（ECM）的调节，我们检测了IL-1对塑料上增殖和生长停滞的X射线照射的人真皮成纤维细胞和包埋在胶原凝胶中的静止细胞中生长因子表达的影响。通过半定量逆转录酶PCR，我们证明IL-1 α和IL-1 β刺激KGF的表达，HGF、IL-1 α、IL-1 β、IL-1 RI和IL-8，而TGF-β则不受影响。组成型mRNA水平通常低于照射后有丝分裂和ECM包埋细胞比增殖的成纤维细胞。在所有三种培养条件下，细胞对IL-1刺激有反应，尽管程度不同，取决于生长因子。如HGF、IL-8和IL-1 β所示，IL-1 α诱导的mRNA表达后，在照射的成纤维细胞中产生和分泌蛋白质。因此，我们的研究结果表明，休息和生长抑制的成纤维细胞，更密切地反映在真皮中的情况，表现出较低的组成性生长因子的表达水平，但特征性地响应IL-1刺激。
Tissue homeostasis in skin is regulated by epithelial-mesenchymal interactions, mostly operating via diffusible factors. To study the underlying regulatory mechanisms, in vitro systems have been established to mimic the in vivo situation in skin, In co-cultures, keratinocytes grow either adjacent to irradiated fibroblasts on plastic or on top of collagen gels containing fibroblasts, thus forming 3-dimensional organotypic structures, Keratinocyte growth is supported in part by fibroblast-produced factors induced by keratinocyte mediators such as interleukin-1 (IL-1). To better understand this cellular interaction and its modulation by fibroblast proliferation and extracellular matrix (ECM), we examined the effect of IL-1 on growth factor expression in proliferating and growth-arrested x-irradiated human dermal fibroblasts on plastic and in resting cells embedded in collagen gels, By semiquantitative reverse transcriptase PCR, we demonstrated that IL-1 alpha and IL-1 beta stimulated the expression of KGF, HGF, IL-1 alpha, IL-1 beta, IL-1RI, and IL-8 in fibroblasts regardless of their physiologic condition, whereas that of TGF-beta remained unaffected. The constitutive mRNA levels were usually lower in irradiated postmitotic and ECM-embedded cells than in proliferating fibroblasts. Cells responded to stimulation with IL-1 under all three culture conditions, although to different degrees depending on the growth factor, As demonstrated for HGF, IL-8, and IL-1 beta, the IL-1 alpha-induced mRNA expression was followed by production and secretion of protein in irradiated fibroblasts. Thus, our findings show that resting and growth-inhibited fibroblasts, reflecting more closely the situation in dermis, exhibit lower constitutive growth factor expression levels but characteristically respond to IL-1 stimulation.