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

• 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

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（Keratinocytes，KC）是其主要成分。KC通过制造角蛋白，作为抵抗外源刺激的保护屏障。由于KC可产生多种细胞因子，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。我们发现紫外线会影响KC产生多种细胞因子，并表明它们参与了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 ...更多信息 紫外线引起的炎症、晒伤主要是由UVB引起的，但已知UVA会增强其反应。为了探讨UVA对KC的这种增强作用是否是由于UVA诱导KC产生细胞因子和PGE_2等促炎介质所致，本实验采用体外培养的正常人KC，分别或同时用UVB和UVA照射。通过逆转录-聚合酶链反应（RT-PCR）方法测定每种细胞因子的mRNA水平，并通过酶联免疫吸附测定（ELISA）或酶免疫测定（EIA）测定培养上清液中的蛋白质产量。UVB（300 J/m^2）照射后24 h可诱导IL-6、IL-8、TNF-α、TGF-β1和GM-CSF mRNA的表达，UVA（10 kJ/m^2）照射后24 h仅诱导IL-6和IL-8 mRNA的表达。UVB和UVA可使IL-1α、IL-6、IL-8和PGE_2的产生相加性增加，但TNF-α、IL-8和PGE_2的产生与UVB和UVA的作用无显著性差异。UVB照射后，细胞培养上清中可检测到TGF-β1和GM-CSF蛋白。这些结果表明，UVB和UVA差异调节IL-衍生的细胞因子的表达和生产和UVA是能够诱导从KC添加到UVB的促炎介质。我们的研究结果解释了UVA增强UVB诱导的皮肤炎症的机制。在我们的实验条件下，UVA诱导了IL-12，这是已知的恢复UVB诱导的免疫抑制，表明UVA可能抑制Less

项目成果

Kondo S.: "The roles of Kelatinocyte-derived cytokines in the epidermis and their possible responses to UVA-irradiation"J Invest Dermatol Symp Bec. 4・2. 177-183 (1999)

Kondo S.：“角质形成细胞衍生的细胞因子在表皮中的作用及其对 UVA 照射的可能反应”J Invest Dermatol Symp Bec 4·2 (1999)。

Kondo S: "The roles of cytokines in photoaging."J Dermatol Sci. 23(Suppl 1). 30-36 (2000)

Kondo S：“细胞因子在光老化中的作用。”J Dermatol Sci。

Kondo S: "The roles of cytokines in photoaging."J Dermatol Sci. 23 (suppl. 1). S30-S36 (2000)

Kondo S：“细胞因子在光老化中的作用。”J Dermatol Sci。

Kondo S, et al: "Dose-dependent induction of IL-12 but not IL-10 from human keratinocytes after exposure to UVA."J Cell Physiol. 177. 493-498 (1998)

Kondo S 等人：“暴露于 UVA 后，人角质形成细胞会剂量依赖性诱导 IL-12，但不会诱导 IL-10。”J Cell Physiol。

Kondo S, Yoneta A, Yazawa H, Kamata A, Jimbow K: "Down-regulation of CXCR-2 but not CXCR-1 expression by human keratinocytes by UVB."J Cell Physiol. 182 (3). 366-370 (2000)

Kondo S、Yoneta A、Yazawa H、Kamata A、Jimbow K：“UVB 下调人类角质形成细胞的 CXCR-2 表达，但不下调 CXCR-1。”J Cell Physiol。