一個新穎的鋅指蛋白在TLR4所扮演之功能探討

The functional role of a novel zinc finger protein in the regulation of TLR4 signaling

蔡惠玫(Hui-Mei Tsai)

指導教授 ： 徐立中

國立臺灣大學/醫學院/分子醫學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.10202

摘要

無資料

關鍵字

先天免疫 ； 鋅指蛋白

並列摘要

Innate immunity is the first-line defense of hosts to combat invading microbes and cellular damages. It is initiated by the activation of various germline-encoded pattern recognition receptors (PRRs) including Toll-lie receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), C-type lectin receptors (CLRs), and PYHIN family. PRRs recognize pathogen-associated molecular patterns (PAMPs) derived from bacteria, viruses and fungi, and damage-associated molecular patterns (DAMPs) from stressed or injured tissues. Activation of TLRs elicits MyD88- and/or TRIF-dependent signaling pathways resulting in the induction of proinflammatory cytokines and type-I interferons. However, both under- or over-expression of these cytokines lead to infectious and inflammatory diseases, respectively, which are dangerous to hosts. Thus, tight regulation of TLRs-mediated immune responses is important. We previously identified a zinc-finger protein—ZFAND5 that was upregulated in LPS stimulated-macrophages. Here, we focused on its role in TLRs-mediated pathways and possible molecular mechanism. We found that the expression of inflammatory cytokines, and type I interferons and interferon-stimulated genes was reduced upon TLR1/2, TLR3, TLR4 and TLR9 activation in ZFAND5-deficient macrophages. Furthermore, ZFAND5 interacted with TRAF3 in response to LPS stimulation. Through domain mapping, we found that the A20-like domain of ZFNAD5 and the TRAF-C domain of TRAF3 were required for their interaction. Taken together, our studies revealed that ZFAND5 involves in TLRs-mediated immune responses possibly through TRAF3.

並列關鍵字

innate immunity ； TLR

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