Ultraviolet B irradiation decreases CXCL10 expression in keratinocytes through endoplasmic reticulum stress
Ultraviolet B irradiation decreases CXCL10 expression in keratinocytes through endoplasmic reticulum stress
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DOI：
10.1002/jcb.29936
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发表时间：
2021-04-28
影响因子：
4
通讯作者：
Matsuguchi, Tetsuya
中科院分区：
文献类型：
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作者：
Ohnishi, Tomokazu;Hisadome, Mitsuhiro;Matsuguchi, Tetsuya
紫外线照射是牛皮癣的标准治疗选择之一。干扰素（IFN）-γ和IFN-γ诱导的CXCL 10是银屑病的治疗靶点，其由银屑病病变中的角质形成细胞高度表达。在这项研究中，我们发现，紫外线B（UVB）照射抑制IFN-γ信号传导事件，包括STAT 1磷酸化和诱导角质形成细胞中CXCL 10信使RNA（mRNA）的表达。IFN-γ诱导的CXCL 10 mRNA在HaCaT细胞、人角质形成细胞系和人上皮角质形成细胞中的表达也被H2 O2或内质网（ER）应激诱导剂抑制。相反，抗氧化剂的混合物，Trolox和抗坏血酸，和ER应激抑制剂salubrinal部分抵消UVB对IFN-γ诱导的CXCL 10 mRNA表达的抑制作用在HaCaT细胞。我们还发现，UVB和ER应激降低了角质形成细胞质膜组分中的IFN-γ受体1蛋白水平。这些观察结果表明，ER应力和活性氧的产生是必不可少的UVB对IFN-γ诱导的角质形成细胞CXCL 10 mRNA的抑制作用。
Ultraviolet radiation is one of the standard treatment selections for psoriasis. interferon (IFN)-gamma and IFN-gamma-induced CXCL10, which are highly expressed by keratinocytes in psoriasis lesion, are therapeutic targets for psoriasis. In this study, we found that ultraviolet B (UVB) irradiation inhibited IFN-gamma signaling events, including STAT1 phosphorylation and induction of CXCL10 messenger RNA (mRNA) expression in keratinocytes. IFN-gamma-induced expression of CXCL10 mRNA in HaCaT cells, a human keratinocyte cell line, and human epithelial keratinocytes were also inhibited by H2O2 or endoplasmic reticulum (ER) stress inducers. Conversely, a mixture of antioxidants, Trolox and ascorbic acid, and the ER stress inhibitor salubrinal partially counteracted the inhibitory effect of UVB on IFN-gamma-induced CXCL10 mRNA expression in HaCaT cells. We also found that UVB and ER stress reduced IFN-gamma receptor 1 protein levels in the plasma membrane fraction of keratinocytes. These observations suggested that ER stress and the generation of reactive oxygen species are essential for the inhibitory effect of UVB on IFN-gamma-induced CXCL10 mRNA in keratinocytes.