Newkirk Kimberly M, Duncan F Jason, Brannick Erin M, Chandler Heather L, Parent Allison E, Kusewitt Donna F
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Lab Invest. 2008 Aug;88(8):831-41. doi: 10.1038/labinvest.2008.37. Epub 2008 May 5.
We previously reported ultraviolet radiation (UVR) induction of Slug, a Snail family zinc-finger transcription factor, in the epidermis of mice; we now report that Slug-knockout mice are, unexpectedly, more resistant to sunburn than wild-type mice. There was a marked difference between the cutaneous inflammatory response in the skin of Slug-knockout and wild-type mice from 12 h to 1 week following a single exposure to 3 minimal erythemal doses of UVR. Slug-knockout mice showed a much reduced immediate increase in skin thickness and neutrophil infiltration compared to wild-type mice. However, there were as many or more intraepidermal T cells, dermal mast cells, and dermal blood vessels in the UVR-exposed skin of Slug-knockout mice as in the skin of wild-type mice. Differences in cytokine and chemokine expression following UVR appeared to account for at least some differences between the genotypes in cutaneous inflammatory response. Despite the reported antiapoptotic and antiproliferative role for Slug in some cell types, we observed little difference between the genotypes in UVR-induced keratinocyte apoptosis or proliferation. Our findings indicate an unexpected but important role for Slug in the acute cutaneous inflammatory response to UVR.
我们之前报道过,在小鼠表皮中紫外线辐射(UVR)可诱导蜗牛家族锌指转录因子Slug;我们现在报道,出乎意料的是,Slug基因敲除小鼠比野生型小鼠对晒伤更具抵抗力。在单次暴露于3个最小红斑量的UVR后,从12小时到1周,Slug基因敲除小鼠和野生型小鼠皮肤中的皮肤炎症反应存在显著差异。与野生型小鼠相比,Slug基因敲除小鼠的皮肤厚度即时增加和中性粒细胞浸润明显减少。然而,在暴露于UVR的Slug基因敲除小鼠皮肤中,表皮内T细胞、真皮肥大细胞和真皮血管的数量与野生型小鼠皮肤中的一样多或更多。UVR后细胞因子和趋化因子表达的差异似乎至少在一定程度上解释了不同基因型在皮肤炎症反应中的一些差异。尽管有报道称Slug在某些细胞类型中具有抗凋亡和抗增殖作用,但我们观察到不同基因型在UVR诱导的角质形成细胞凋亡或增殖方面几乎没有差异。我们的研究结果表明,Slug在对UVR的急性皮肤炎症反应中具有意想不到但重要的作用。