肿瘤坏死因子α
促炎细胞因子
髓样
癌症研究
细胞因子
金属蛋白酶
免疫学
生物
炎症
医学
化学
基质金属蛋白酶
生物化学
作者
Keisuke Horiuchi,Takehiro Kimura,Takeshi Miyamoto,Hironari Takaishi,Yasunori Okada,Yoshiaki Toyama,Carl Blobel
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2007-09-01
卷期号:179 (5): 2686-2689
被引量:298
标识
DOI:10.4049/jimmunol.179.5.2686
摘要
Abstract TNF-α, a potent proinflammatory cytokine, is synthesized as a membrane-anchored precursor and proteolytically released from cells. Soluble TNF is the primary mediator of pathologies such as rheumatoid arthritis, Crohn’s disease, and endotoxin shock. The TNF-α converting enzyme (TACE), a disintegrin and metalloprotease 17 (ADAM17), has emerged as the best candidate TNF sheddase, but other proteinases can also release TNF. Because TACE-deficient mice die shortly after birth, we generated conditional TACE-deficient mice to address whether TACE is the relevant sheddase for TNF in adult mice. In this study, we report that TACE inactivation in myeloid cells or temporal inactivation at 6 wk offers strong protection from endotoxin shock lethality in mice by preventing increased TNF serum levels. These findings corroborate that TACE is the major endotoxin-stimulated TNF sheddase in mouse myeloid cells in vivo, thereby further validating TACE as a principal target for the treatment of TNF-dependent pathologies.
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