Characterization of PKR function in TLR4 signaling

• Main Authors: Tzu-Ting Tseng, 曾慈婷
• Other Authors: Li-Chung Hsu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/06431182034151509611

碩士 === 臺灣大學 === 分子醫學研究所 === 98 === Innate immunity is of great importance not only in host defense against infections, but also has been implicated in development and tissue homeostasis. Immune cells, such as macrophages, use pattern-recognition receptors (PRR) to sense microbes and dying cells and initiate inflammatory response that helps to fight the pathogen and assist tissue repair. However, the inflammation process must be finely tuned or it may turn out to be pathogenic. Among several classes of PRR, the mammalian TLR (Toll-like receptor) family comprises 13 membrane receptors which are able to recognize a range of conserved microbial motifs termed PAMPs (pathogen-associated molecular patterns) or endogenous DAMPs (danger-associated molecular patterns) released by stressed or damaged tissues and activate immune response. PKR (dsRNA-dependent protein kinase) has been shown to be involved in IFNβ production and apoptosis in LPS-induced macrophages previously [1]. In this study we further characterize the functional role of PKR in the TLR4 signaling pathway. We found that TBK1 regulates PKR activation, which in turn enhances TBK1 kinase activity. We also demonstrated that PKR is required for maintaining the integrity of TRIF-TRAF3-TBK1 complex. Our findings further delineate the TLR4-TRIF signaling pathway after LPS stimulation, and could shed some light in advanced understanding of certain inflammatory and infectious diseases and development of therapies.