Effects of UVA on the expression of keratinocyte-derived cytokines and immune suppression

皮肤是最大的器官，覆盖了整个体表。角质形成细胞（KC）是其主要成分。KC通过制造角蛋白，对外源刺激起到保护屏障的作用。由于KC已被证明可以产生多种细胞因子，皮肤在机体的免疫和炎症反应中起着重要的作用。细胞因子影响其他细胞和器官，介导细胞生长和分化以及炎症和免疫反应。因此，细胞因子维持细胞和细胞间的稳态。在各种皮肤疾病中检测到细胞因子的失调和异常产生。越来越多的证据表明细胞因子对某些疾病的发病机制或严重程度有重要作用。我们发现紫外线影响KC产生多种细胞因子，并提示它们参与皮肤暴露在阳光下的各种病理生理状况，包括红斑形成，免疫抑制，致癌和光老化。uvr引起的炎症，晒伤，主要是由UVB引起的，但众所周知UVA会增强其反应。为了研究UVA的增强作用是否由于UVA对KC产生促炎介质（包括细胞因子和PGE_2）的作用，我们分别用UVB和UVA分别或同时照射正常人KC。采用逆转录聚合酶链反应（RT-PCR）法检测各细胞因子mRNA水平，采用酶联免疫吸附法（ELISA）或酶免疫分析法（EIA）检测培养上清蛋白产量。300 J/m^2的UVB照射后24 h诱导IL-6、IL-8、TNF-α、TGF-β1和GM-CSF mRNA的表达，而在10 kJ/m^2的UVA照射后24 h仅观察到IL-6和IL-8 mRNA水平的升高。UVB和UVA均能显著提高IL-1α、IL-6、IL-8和PGE_2的生成，但TNF-α水平显著升高。UVB照射后检测培养上清中TGF-β1和GM-CSF蛋白。这些结果表明，UVB和UVA对il源性细胞因子的表达和产生有不同的调节作用，UVA可以在UVB的基础上诱导KC产生促炎介质。我们的研究结果解释了UVA增强uvb诱导的皮肤炎症的机制。IL-12可以恢复uvb诱导的免疫抑制，在我们的实验条件下UVA诱导IL-12，提示UVA可能抑制Less

Skin is the largest organ, covering the entire body surface. Keratinocytes (KC) are its major component. The KC, by making keratin protein, function as a protective barrier against exogenous stimuli. As KC have been demonstrated to produce various kinds of cytokines, skin plays an important role in immunologic and inflammatory responses of the body. Cytokines affect other cells and organs, mediating cellular growth and differentiation as well as inflammation and immune reactions. Thus, cytokines maintain the cellular and intercellular homeostasis. Dysregulation and abnormal production of cytokines are detected in various skin diseases. Evidence is accumulating to show the significant contribution of cytokines to the pathogenesis or severity of certain diseases. We have found that ultraviolet light affects KC to produce a variety of cytokines, and suggested that they are involved in various pathophysiologic conditions observed in the skin exposed to sunlight including erythema formation … More , immune suppression, carcinogenesis and photoaging.UVR-induced inflammation, sunburn, is mainly induced by UVB, but UVA is known to augment its reaction. In order to find if this augmentative effect of UVA is due to the effect of UVA on KC to induce proinflammatory mediators including cytokines and PGE_2, normal human KC were cultured and irradiated by UVB and UVA either separately or concomitantly. Levels of mRNA for each cytokine were determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method and protein production in cultured supernatants was assayed by enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassay (EIA). UVB (300 J/m^2) induced the expression of IL-6, IL-8, TNF-α, TGF-β1 and GM-CSF mRNA at 24 h after irradiation, while an increase only in IL-6 and IL-8 mRNA levels was observed at 24 h after UVA irradiation (10 kJ/m^2). IL-1α, IL-6, IL-8 and PGE_2 production was increased additively by UVB and UVA, but significant levels of TNF-α., TGF-β1 and GM-CSF protein in cultured supernatants were detected only after UVB irradiation. These results indicate that UVB and UVA differentially regulate the expression and production of IL-derived cytokines and UVA is able to induce proinflammatory mediators from KC additively to UVB.Our results explain the mechanism by which UVA augments UVB-induced skin inflammation. IL-12, which is known to restore UVB-induced immune suppression, was induecd by UVA under our experimental condition suggesting that UVA may inhibit Less