Grandjean-Laquerriere Alexia, Antonicelli Frank, Gangloff Sophie C, Guenounou Moncef, Le Naour Richard
Laboratoire d'Immunologie et de Microbiologie, IPCM, EA3796, IFR53, UFR de Pharmacie, 1 rue du Maréchal Juin, 51096 Reims Cedex, France.
Cytokine. 2007 Jan;37(1):76-83. doi: 10.1016/j.cyto.2007.02.020. Epub 2007 Mar 30.
In the present study, we investigated the implication of NF-kappaB in the production of pro-inflammatory cytokine IL-18 by human keratinocytes stimulated by UVB. We demonstrated that NCTC 2544 keratinocyte cell line irradiated by UVB enhanced the IL-18 mRNA and protein secretion under its bioactive form. Overexpression of IL-18 by UVB irradiation was accompanied by NF-kappaB transcription factor activation using specific IL-18 gene sequence corresponding to NF-kappaB DNA binding site. The relationship between these transcription factors and IL-18 expression was confirmed using curcumin and PDTC, two inhibitors of NF-kappaB. Our results show that UVB and curcumin or PDTC co-treatment led to a down-regulation of IL-18 expression associated with an inhibition of NF-kappaB DNA binding. Hence, our results demonstrated that this transcription factor is implicated in biologically active IL-18 production by human keratinocytes irradiated by UVB.
在本研究中，我们调查了核因子-κB（NF-κB）在紫外线B（UVB）刺激的人角质形成细胞产生促炎细胞因子白细胞介素-18（IL-18）中的作用。我们证明，经UVB照射的NCTC 2544角质形成细胞系在其生物活性形式下增强了IL-18信使核糖核酸（mRNA）和蛋白质分泌。利用与NF-κB DNA结合位点相对应的特定IL-18基因序列，UVB照射导致的IL-18过表达伴随着NF-κB转录因子激活。使用NF-κB的两种抑制剂姜黄素和吡咯烷二硫代氨基甲酸盐（PDTC）证实了这些转录因子与IL-18表达之间的关系。我们的结果表明，UVB与姜黄素或PDTC共同处理导致IL-18表达下调，并伴有NF-κB DNA结合的抑制。因此，我们的结果表明，该转录因子参与了UVB照射的人角质形成细胞产生生物活性IL-18的过程。
