ADAM10型
去整合素
肿瘤坏死因子α
金属蛋白酶
细胞生物学
化学
生物
分子生物学
基质金属蛋白酶
免疫学
生物化学
作者
Atsuhiko Hikita,Nobuho Tanaka,Shoji Yamane,Yasuko Ikeda,Hiroshi Furukawa,Shigeto Tohma,Ryuji Suzuki,Sakae Tanaka,Hiroyuki Mitomi,Naoshi Fukui
摘要
Tumor necrosis factor-α (TNF-α) is initially synthesized as a membrane-bound protein and converted into a soluble form by proteolytic cleavage. Although a disintegrin and metalloproteinase 17 (ADAM17) is considered to be the primary sheddase for TNF-α, it is not known whether ADAM17 is solely responsible for that process in any type of cells. To identify the TNF-α sheddase(s) in varieties of cells, we performed experiments using a unique screening system and observed that ADAM9, ADAM10, ADAM17, and ADAM19 were capable of cleaving TNF-α. We then performed RNA interference experiments and confirmed that ADAM10 and ADAM17 were in fact involved in TNF-α shedding in 293A cells. In mouse macrophages, ADAM17 was confirmed to be the primary sheddase, but the involvement of ADAM10 was also demonstrated. In NIH3T3 cells, ADAM10 could be more important in the shedding than ADAM17. In mouse vascular endothelial cell line UV♀2, ADAM10 and ADAM17 were equally involved in TNF-α shedding, whereas ADAM17 was a major sheddase in human osteoarthritic chondrocytes. From these observations and others, we concluded that both ADAM10 and ADAM17 can be a TNF-α sheddase and that their significance could be determined by their expression levels and the abundance of tissue inhibitor of metalloproteinases.
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