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

UVA对角质形成细胞源性细胞因子表达及免疫抑制的影响

基本信息

批准号：
10670800
负责人：
KONDO Seiji
金额：
$ 0.9万
依托单位：
SAPPORO MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670800/
关键词：
UVA UVB IL-12 immunosuppression cytokine keratinocytes アポトーシスケモカイン CXCR-2 CXCR-1 ケラチノサイト IL-12 IL-10 紫外線免疫抑制

项目摘要

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

皮肤是最大的器官，覆盖整个身体表面。角质形成细胞（KC）是其主要成分。KC 可以产生角蛋白，起到抵御外源刺激的保护屏障的作用。皮肤在身体的免疫和炎症反应中发挥着重要作用，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。在各种皮肤疾病中都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显着影响。我们发现紫外线会影响 KC 产生多种细胞因子。它们参与在暴露于阳光下的皮肤中观察到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UVA是为了查明 UVA 的这种增强作用是否是由于 UVA 对 KC 诱导促炎介质（包括细胞因子和 PGE_2）的影响，对正常人 KC 进行了培养，并分别或同时接受 UVB 和 UVA 照射。通过逆转录酶-聚合酶链式反应 (RT-PCR) 方法测定每种细胞因子的 mRNA 水平，并通过酶联法测定培养上清液中的蛋白质产量。照射后24小时，免疫吸附测定（ELISA）或酶联免疫测定（EIA）（300 J/m^2）诱导IL-6、IL-8、TNF-α、TGF-β1和GM-CSF mRNA的表达。，而 UVA 照射（10 kJ/m^2）后 24 小时仅观察到 IL-6 和 IL-8 mRNA 水平增加。 UVB 和 UVA 使 IL-8 和 PGE_2 产量增加，但仅在 UVB 照射后才检测到培养上清液中 TNF-α、TGF-β1 和 GM-CSF 蛋白的显着水平。这些结果表明 UVB 和 UVA 具有差异调节作用。 IL 衍生细胞因子和 UVA 的表达和产生能够诱导 KC 和 UVB 等促炎介质。我们的结果解释了 UVA 增强 UVB 诱导的皮肤炎症的机制。 IL-12 已知可恢复 UVB 诱导的免疫抑制，在我们的实验条件下由 UVA 诱导，表明 UVA 可能抑制 Less