siRNA knockdown of ADAM-10, but not ADAM-17, significantly reduces fractalkine shedding following pro-inflammatory cytokine treatment in a human adult brain endothelial cell line

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• 作者：Louise A. Hurst ; Rowena A.D. Bunning ; Basil Sharrack ; M. Nicola Woodroofe
• 关键词：Fractalkine ; ADAM-10 ; ADAM-17 ; siRNA ; Endothelial cells ; hCMEC/D3
• 刊名：Neuroscience Letters
• 出版年：2012
• 出版时间：11 July, 2012
• 年：2012
• 卷：521
• 期：1
• 页码：52-56
• 全文大小：360 K

文摘

Fractalkine shedding is believed to occur constitutively and following induction via the activity of two membrane-bound enzymes, ADAM-10 and ADAM-17. However, our previous work suggested that ADAM-17 is not involved in the proteolytic release of fractalkine under TNF treatment of a human adult brain endothelial cell line, hCMEC/D3. The pro-inflammatory cytokine, TNF, has previously been shown to be expressed in the perivascular cuffs in multiple sclerosis. Here we sought to identify, using siRNAs to silence the expression of ADAM-10 and ADAM-17, whether ADAM-10 is responsible for TNF-induced shedding of fractalkine from the cell membrane in hCMEC/D3. Our findings suggest that ADAM-10, and not ADAM-17, is the major protease involved in fractalkine release under pro-inflammatory conditions in this human adult brain endothelial cell model.