ADAM17 regulates TNF-α expression upon lipopolysaccharide stimulation in oral keratinocytes
ADAM17 regulates TNF-α expression upon lipopolysaccharide stimulation in oral keratinocytes
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DOI：
10.2220/biomedres.38.157
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发表时间：
2017-01-01
影响因子：
1.2
通讯作者：
Ansai, Toshihiro
中科院分区：
文献类型：
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作者：
Hirayama, Aya;Awano, Shuji;Ansai, Toshihiro
去整合素和金属蛋白酶17（ADAM17）是肿瘤坏死因子（TNF）转化酶，并且首先被鉴定为切割TNF-α的前结构域的酶，TNF-α是一种促炎细胞因子，在破坏性牙周病的免疫调节和各种炎症反应中起核心作用。本研究的目的是验证牙龈上皮中是否存在ADAM 17，并阐明其参与口腔角质形成细胞中TNF-α的释放。在从患者和人口腔角质形成细胞（HOK）获得的牙龈组织中进行ADAM 17的免疫组织化学分析。此外，TNF-α和ADAM17的HOK暴露于脂多糖（LPS）的水平进行了评估，使用酶联免疫吸附试验。此外，评估了ADAM 17抑制剂、基质金属蛋白酶（MMP）抑制剂和ADAM 17 siRNA对TNF-α浓度的影响。在发炎牙龈组织和HOKs的上皮中观察到强烈的ADAM 17免疫反应性。此外，用ADAM17抑制剂或ADAM17 siRNA处理抑制HOK中由LPS诱导的TNF-α的产生。目前的研究表明，ADAM17是强烈表达的牙龈组织的上皮细胞，并表明，ADAM17可能是一个关键酶，调节肿瘤坏死因子-α在口腔角质形成细胞的产生。
A disintegrin and metalloprotease 17 (ADAM17) is a tumor necrosis factor (TNF)-converting enzyme and was first identified as the enzyme that cleaves the prodomain of TNF-alpha, a proinflammatory cytokine that plays a central role in immune regulation and a variety of inflammatory responses in destructive periodontal disease. The aim of the present study was to verify the presence of ADAM17 in the gingival epithelium and elucidate its involvement in the release of TNF-alpha in oral keratinocytes. Immunohistochemical analyses of ADAM17 were performed in gingival tissues obtained from patients and in human oral keratinocytes (HOKs). Additionally, levels of TNF-alpha and ADAM17 in HOKs exposed to lipopolysaccharide (LPS) were assessed using enzyme-linked immunosorbent assays. Moreover, the effects of ADAM17 inhibitor, matrix metalloproteinase (MMP) inhibitor, and ADAM17 siRNA on TNF-alpha concentration were assessed. Strong immunoreactivity for ADAM17 was observed in the epithelium of the inflamed gingival tissues and in HOKs. Furthermore, treatment with either ADAM17 inhibitor or ADAM17 siRNA inhibited the generation of TNF-alpha induced by LPS in HOKs. The present study demonstrates that ADAM17 is strongly expressed in the epithelium of gingival tissues and suggests that ADAM17 may be a key enzyme that regulates the generation of TNF-alpha in oral keratinocytes.