G2A plays proinflammatory roles in human keratinocytes under oxidative stress as a receptor for 9-hydroxyoctadecadienoic acid
G2A plays proinflammatory roles in human keratinocytes under oxidative stress as a receptor for 9-hydroxyoctadecadienoic acid
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DOI：
10.1038/sj.jid.5701172
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发表时间：
2008-05-01
影响因子：
6.5
通讯作者：
Izumi, Takashi
中科院分区：
文献类型：
--
作者：
Hattori, Tomoyasu;Obinata, Hideru;Izumi, Takashi
G2 A是氧化游离脂肪酸（如9-羟基十八碳二烯酸（HODE））的应激诱导的G蛋白偶联受体。由于皮肤常规和病理暴露于许多氧化应激，如紫外线辐射，化学试剂和炎症，可能会诱导G2 A的表达和G2 A配体的生产，我们研究了G2 A在人类角质形成细胞的功能。G2 A在人表皮、正常人表皮角质形成细胞（NHEK）和永生化人角质形成细胞系（HaCaT）中表达。9（S）-HODE在NHEK细胞中诱发细胞内钙动员和细胞因子（包括IL-6、IL-8和GM-CSF）的分泌。通过G2 A的过表达，这些反应在HaCaT细胞中变得突出。9（S）-HODE通过抑制DNA合成和将细胞周期阻滞在G 0/1期来抑制NHEK细胞的增殖。另一方面，13（S）-HODE，另一个主要的氧化产物，从亚油酸酯，表现出很少或没有影响的细胞因子分泌或对NHEK细胞的增殖。设计用于下调G2 A的小干扰RNA导致9（S）-HODE诱导的对NHEK细胞增殖的抑制作用的抑制。UVB和H_2O_2诱导HaCaT细胞G_2A表达，并引起亚油酸氧化产生9-HODE。这些结果表明，9-HODE-G2 A信号在氧化条件下的皮肤中起促炎作用。
G2A is a stress-inducible G protein-coupled receptor for oxidized free fatty acids, such as 9-hydroxyoctadecadienoic acid (HODE). As skin is routinely and pathologically exposed to many oxidative stresses such as UV radiation, chemical agents, and inflammation that might induce both G2A expression and production of G2A ligands, we examined G2A function in human keratinocytes. G2A was expressed in human epidermis, normal human epidermal keratinocytes (NHEK), and an immortalized human keratinocyte cell line (HaCaT). 9(S)-HODE evoked intracellular calcium mobilization and secretion of cytokines, including IL-6, IL-8, and GM-CSF in NHEK cells. These responses became prominent in HaCaT cells by overexpression of G2A. 9(S)-HODE inhibited proliferation of NHEK cells by suppressing DNA synthesis and arresting the cell cycle in the G0/1-phase. On the other hand, 13(S)-HODE, another major oxidative product from linoleate, showed little or no effect on either cytokine secretion or on proliferation in NHEK cells. A small interfering RNA designed to downregulate G2A caused suppression of 9(S)-HODE-induced inhibitory effects on proliferation of NHEK cells. UVB and H2O2 induced G2A expression and caused oxidation of linoleate to produce 9-HODE in HaCaT cells. These results suggest that 9-HODE-G2A signaling plays proinflammatory roles in skin under oxidative conditions.