Wlaschek M, Bolsen K, Herrmann G, Schwarz A, Wilmroth F, Heinrich P C, Goerz G, Scharffetter-Kochanek K
Department of Dermatology, University of Düsseldorf, F.R.G.
J Invest Dermatol. 1993 Aug;101(2):164-8. doi: 10.1111/1523-1747.ep12363644.
Like other cytokines, IL-6 has been reported to stimulate collagenase. In this study we were interested in whether IL-6 is involved in the ultraviolet (UV) mediated up-regulation of fibroblast-derived collagenase. Confluent fibroblast monolayers were irradiated under standardized conditions. Following UVA irradiation the bioactivity of IL-6 increased up to fiftyfold in the supernatants of irradiated compared to mock-irradiated fibroblasts. As determined by Northern blot analysis this was also reflected on the pre-translational level by a tenfold increase of IL-6-specific mRNA following UVA irradiation. Induction of IL-6-specific mRNA was maximal at 6 h post-irradiation, thus clearly preceding the maximal induction of collagenase mRNA at 24 h post-irradiation. To elucidate the regulatory role of IL-6 in the UVA induction of fibroblast-derived collagenase, monospecific polyclonal neutralizing antibodies directed against recombinant human IL-6 and antisense oligonucleotides specifically inhibiting the translation of IL-6 mRNA were used at various concentrations. The amount of UVA-induced collagenase mRNA was reduced in a dose-dependent manner when antibodies or specific antisense oligonucleotides were present during and after irradiation. Taken together our data provide first evidence that UVA enhances IL-6 synthesis and secretion in fibroblasts. IL-6 induces via an autocrine mechanism collagenase and may thus contribute to the actinic damage of the dermis.
与其他细胞因子一样，据报道白细胞介素-6（IL-6）可刺激胶原酶。在本研究中，我们感兴趣的是IL-6是否参与紫外线（UV）介导的成纤维细胞源性胶原酶的上调。在标准化条件下对汇合的成纤维细胞单层进行照射。与假照射的成纤维细胞相比，UVA照射后，照射后的成纤维细胞上清液中IL-6的生物活性增加了高达50倍。通过Northern印迹分析确定，这在翻译前水平上也有所体现，即UVA照射后IL-6特异性mRNA增加了10倍。IL-6特异性mRNA的诱导在照射后6小时达到最大值，明显早于照射后24小时胶原酶mRNA的最大诱导。为了阐明IL-6在UVA诱导成纤维细胞源性胶原酶中的调节作用，使用了针对重组人IL-6的单特异性多克隆中和抗体和特异性抑制IL-6 mRNA翻译的反义寡核苷酸，浓度各不相同。当在照射期间和照射后存在抗体或特异性反义寡核苷酸时，UVA诱导的胶原酶mRNA的量以剂量依赖性方式减少。综上所述，我们的数据首次证明UVA可增强成纤维细胞中IL-6的合成和分泌。IL-6通过自分泌机制诱导胶原酶，因此可能导致真皮的光化性损伤。
