| 背景 | Toll-like receptor 4 is a ~95 kDa protein. Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways. At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production. 1. Arbour, NC. et al. (2000) Nature genetics 25, 187-91. PMID: 108356342. Bulut, Y. et al. (2005) The Journal of biological chemistry 280, 20961-7. PMID: 158093033. Jung, SB. et al. (2006) Infection and immunity 74, 2686-96. PMID: 166222055. Kim, F. et al. (2007) Circulation research 100, 1589-96. PMID: 174787296. Stewart, CR. et al. (2010) Nature immunology 11, 155-61. PMID: 200375847. Schmidt, M. et al. (2010) Nature immunology 11, 814-9. PMID: 207111928. Estruch, M. et al. (2013) Atherosclerosis 229, 356-62. PMID: 238801879. Tatematsu, M. et al. (2016) Journal of immunology (Baltimore, Md. : 1950) 196, 3865-76. PMID: 2702219510. Xiahou, Z. et al. (2017) Nature communications 8, 950. PMID: 29038465 |
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