Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes.
Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes.
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UVB 诱导的活性氧参与角质形成细胞的 TGF-β 生物合成和激活。
DOI：
10.1016/j.freeradbiomed.2004.12.005
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发表时间：
2005
影响因子：
7.4
通讯作者：
Kochevar,IreneE
中科院分区：
文献类型：
--
作者：
Wang,Hongjun;Kochevar,IreneE
由角质形成细胞响应UVB（290-320 nm）产生的TGF-β是急性和慢性太阳辐射对皮肤影响的潜在介质。本研究旨在确定活性氧（ROS）是否介导UVB诱导的角质形成细胞中TGF-β的生物合成以及随后潜在的TGF-β复合物的活化。UVB照射提高角质形成细胞上清液中的总TGF-β（潜伏加活性）和活性TGF-β，其中活性形式的增加更大。UVB照射诱导ROS增加30%，照射后90分钟检测到ROS。细胞内活性氧清除剂NAC和Trolox可消除UVB诱导的TGF-β和细胞内活性氧，提示UVB诱导的活性氧参与了TGF-β的调节。NADPH氧化酶活性的抑制剂DPI和夹竹桃苷降低UVB诱导的ROS。NADPH氧化酶活性的增加由EGFR激活介导。UVB诱导的ROS也通过刺激MMP-2和MMP-9的活性激活潜在的TGF-β复合物。总之，生理剂量的UVB增加细胞内ROS，其通过增加MMP的活性上调TGF-β的生物合成和TGF-β的活化。
TGF-β produced by keratinocytes in response to UVB (290–320 nm) is a potential mediator for effects of acute and chronic solar radiation on skin. This study was designed to determine whether reactive oxygen species (ROS) mediate UVB-induced TGF-β biosynthesis in keratinocytes and the subsequent activation of the latent TGF-β complex. UVB irradiation elevated both total (latent plus active) and active TGF-β in the keratinocyte supernatants, with a greater increase in the active form. UVB irradiation induced up to a 30% increase in ROS, and the ROS were detected up to 90 min after irradiation. NAC and Trolox, cytoplasmic ROS scavengers, abolished the UVB-induced TGF-β and intracellular ROS, suggesting that UVB-induced ROS are involved in TGF-β regulation. Inhibitors of NADPH oxidase activity, DPI and apocynin, decreased UVB-induced ROS. The increase in NADPH oxidase activity was mediated by EGFR activation. UVB-induced ROS also activated latent TGF-β complex by stimulating MMP-2 and -9 activities. In summary, physiological doses of UVB increase intracellular ROS, which upregulate TGF-β biosynthesis and activation of TGF-β through increased activity of MMPs.