Differential regulation of interleukin-8 gene transcription by death receptor 3 (DR3) and type I TNF receptor (TNFRI)

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• 作者：Wenlynn B. Su ; Ying-Hsin Chang ; Wan-Wan Lin and Shie-Liang Hsieh
• 关键词：DR3 signaling ; IL-8 secretion
• 刊名：Experimental Cell Research
• 出版年：2006
• 出版时间：1 February 2006
• 年：2006
• 卷：312
• 期：3
• 页码：266-277
• 全文大小：565 K

文摘

TL1A induces interleukin-8 (IL-8) secretion in human peripheral blood monocyte-derived macrophage in a dose- and time-dependent manner. Overexpression of its cognate receptor DR3 can induce a higher amount of IL-8 protein secretion than that induced by TNFRI even though both receptors activate IL-8 gene transcription in a similar fashion. The underlying mechanism for the regulation of the IL-8 gene transcription by DR3 has not been investigated yet. Here, we used HEK293 cells as a model system to dissect the possible signaling components that are involved in the regulation of DR3-mediated IL-8 gene expression. Although both DR3 and TNFRI activated TRAF2 and NF-κB to induce IL-8 gene transcription, the kinase cascades that transduce signals for DR3- and TNFRI-induced IL-8 gene transcription are different. The axis TAK1/ASK1-MKK4/MKK7-JNK2 is responsible for DR3-mediated IL-8 gene expression whereas the axis ASK1-MKK4-JNK1/JNK2/p38MAPK is the choice for TNFRI-mediated activation of IL-8 gene expression. This indicates that the downstream signaling pathways of DR3 and TNFRI for IL-8 secretion are divergent even though both receptors contain death-domain and induce IL-8 secretion via TRAF2.