Mauviel A, Lapière J C, Halcin C, Evans C H, Uitto J
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
J Biol Chem. 1994 Jan 7;269(1):25-8.
Type VII collagen is the major component of anchoring fibrils in the cutaneous basement membrane zone. In this study, we have examined the effects of various cytokines on the expression of types I and VII collagen genes in dermal fibroblasts in culture. The pro-inflammatory cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and leukoregulin (LR) strongly elevated (approximately 5-9-fold) type VII collagen mRNA levels, as measured by Northern blot hybridizations. These effects were also observed at the protein level by indirect immunofluorescence using a monoclonal antibody specific for type VII collagen. By contrast, IL-1 beta had only a slight stimulatory effect (approximately 2-fold) on type I collagen gene expression, while TNF-alpha and LR markedly reduced type I collagen mRNA steady-state levels. Interestingly, IL-1, TNF-alpha and LR had additive effects with transforming growth factor-beta (TGF-beta) on type VII collagen gene expression, whereas they counteracted the up-regulatory effect of TGF-beta on type I collagen gene expression. Thus, our data indicate that the modulation of type I and type VII collagen gene expression by cytokines involves different regulatory pathways.
VII型胶原蛋白是皮肤基底膜区锚定原纤维的主要成分。在本研究中，我们检测了多种细胞因子对培养的真皮成纤维细胞中I型和VII型胶原蛋白基因表达的影响。通过Northern印迹杂交检测，促炎细胞因子白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞调节素（LR）可使VII型胶原蛋白mRNA水平显著升高（约5-9倍）。使用针对VII型胶原蛋白的单克隆抗体通过间接免疫荧光在蛋白质水平也观察到了这些效应。相比之下，IL-1β对I型胶原蛋白基因表达仅有轻微的刺激作用（约2倍），而TNF-α和LR则显著降低I型胶原蛋白mRNA的稳态水平。有趣的是，IL-1、TNF-α和LR在VII型胶原蛋白基因表达方面与转化生长因子-β（TGF-β）具有相加作用，而在I型胶原蛋白基因表达方面它们则抵消了TGF-β的上调作用。因此，我们的数据表明细胞因子对I型和VII型胶原蛋白基因表达的调节涉及不同的调控途径。
