ADAM28 is elevated in humans with the metabolic syndrome and is a novel sheddase of human tumour necrosis factor-α.
ADAM28 is elevated in humans with the metabolic syndrome and is a novel sheddase of human tumour necrosis factor-α.
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DOI：
10.1038/icb.2012.44
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发表时间：
2012-11
影响因子：
4
通讯作者：
Matthews, Vance B.
中科院分区：
文献类型：
--
作者：
Jowett, Jeremy B. M.;Okada, Yasunori;Leedman, Peter J.;Curran, Joanne E.;Johnson, Matthew P.;Moses, Eric K.;Goring, Harald H. H.;Mochizuki, Satsuki;Blangero, John;Stone, Leah;Allen, Holly;Mitchell, Chris;Matthews, Vance B.
金属蛋白酶参与从细胞表面切割许多促炎介质。有趣的是，TNF-α水平升高与代谢综合征相关。我们的目的是确定人金属蛋白酶ADAM 28是否与代谢综合征的参数相关，以及ADAM 28是否是一种新的人TNF-α的脱落酶。为了鉴定与代谢综合征相关的新型金属蛋白酶，我们对来自一个特征良好的人类队列的外周血单核细胞进行了微阵列研究。人ADAM 28和TNF-α过表达，siRNA或药物抑制可降低ADAM 28的表达或活性。ELISA法测定细胞上清液中TNF-α水平。我们还在人THP 1巨噬细胞中进行了ADAM 28抑制研究。人ADAM 28表达水平与代谢综合征参数呈正相关。当人ADAM 28和TNF-α在HEK 293细胞中过表达时，两种蛋白质共定位，共免疫沉淀并促进TNF-α脱落。当ADAM 28活性被抑制或ADAM 28表达被下调时，脱落显著减少。在人THP-1巨噬细胞中，内源性ADAM 28和TNF-α共表达，当通过药物抑制或siRNA敲低来抑制ADAM 28时，TNF-α的脱落显著减少。我们的数据表明金属蛋白酶ADAM 28在炎症、肥胖和2型糖尿病中的新机制作用。
Metalloproteinases are implicated in cleaving numerous pro-inflammatory mediators from the cell surface. Interestingly, elevated levels of TNF-α have been associated with the metabolic syndrome. We aimed to ascertain whether the human metalloproteinase ADAM28 correlates with parameters of the metabolic syndrome and if ADAM28 is a novel sheddase of human TNF-α. To identify novel metalloproteinases associated with the metabolic syndrome, we conducted micro-array studies on peripheral blood mononuclear cells from a well characterised human cohort. Human ADAM28 and TNF-α were over-expressed and ADAM28 expression or activity was reduced with siRNA or pharmacological inhibition. TNF-α levels were measured in cell supernatant by ELISA. We also conducted ADAM28 inhibition studies in human THP1 macrophages. Human ADAM28 expression levels were positively correlated with parameters of the metabolic syndrome. When human ADAM28 and TNF-α were over-expressed in HEK293 cells, both proteins co-localised, co-immunoprecipitated and promoted TNF-α shedding. The shedding was significantly reduced when ADAM28 activity was inhibited or ADAM28 expression was down-regulated. In human THP-1 macrophages, endogenous ADAM28 and TNF-α were co-expressed and TNF-α shedding was significantly reduced when ADAM28 was inhibited by pharmacological inhibition or siRNA knock-down. Our data suggests a novel mechanistic role for the metalloproteinase ADAM28 in inflammation, obesity and type 2 diabetes.
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影响因子：
120.7
作者：
Flegal, KM;Carroll, MD;Johnson, CL
通讯作者：
Johnson, CL
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
7.7
作者：
Delibegovic M;Zimmer D;Kauffman C;Rak K;Hong EG;Cho YR;Kim JK;Kahn BB;Neel BG;Bence KK
通讯作者：
Bence KK
DOI：
10.1016/j.bbrc.2009.06.052
发表时间：
2009-08-21
影响因子：
3.1
作者：
Hikichi, Yuichi;Yoshimura, Koji;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu
影响因子：
3.9
作者：
Qian, Mingxin;Bai, Stephen A.;Christ, David D.
通讯作者：
Christ, David D.