TLR4
Toll样受体4（英語：Toll-like receptor 4, 缩写：TLR4），也被称为CD284（分化簇284，cluster of differentiation 284），是先天免疫反应的关键激活因子，在抵抗细菌感染中发挥着核心作用。TLR4是一种跨膜蛋白，分子量约为95 kDa，由TLR4基因编码。
TLR4属于Toll样受体（TLR）家族，该家族是模式识别受体 (PRR) 中的代表。PRR之所以得名，是因为它们能够识别微生物（细菌、病毒、真菌和寄生虫）进化上保守的成分，即病原相关分子模式 (PAMP)。PRR识别PAMP后，会迅速激活先天免疫，这对于抵抗传染病至关重要。[5]
TLR4主要在髓系来源的免疫细胞中表达，包括单核细胞、巨噬细胞和树突状细胞（DC）[5]。它也在一些非免疫细胞上低水平表达，例如上皮细胞、内皮细胞、胎盘细胞和胰岛β细胞。大多数髓系细胞还表达大量的质膜锚定CD14，CD14促进脂多糖（LPS）激活TLR4，并控制脂多糖激活的TLR4的后续内吞作用，这对于受体信号传导和降解至关重要[6][7]。
TLR4的主要配体是脂多糖（LPS），它是革兰氏阴性菌和某些革兰氏阳性菌外膜的主要成分。TLR4也可被称为损伤相关分子模式 (DAMP) 的内源性化合物激活，包括高迁移率族蛋白1 (HMGB1)、S100蛋白或组蛋白。这些化合物在组织损伤期间以及细胞死亡或坏死时释放。[8][9][10][11][12]
TLR4是模式识别受体中Toll样受体（TLR）家族的成员，可结合其配体脂多糖（LPS）激活NF-κB信号通路，在先天免疫系統中起到重要作用[5]。
参考文献
- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000136869 – Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000039005 – Ensembl, 2017年5月
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 5.0 5.1 5.2 Vaure C, Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Frontiers in Immunology. 2014, 5: 316. PMC 4090903
. PMID 25071777. doi:10.3389/fimmu.2014.00316 .
- ^ Mahnke K, Becher E, Ricciardi-Castagnoli P, Luger TA, Schwarz T, Grabbe S. CD14 is Expressed by Subsets of Murine Dendritic Cells and Upregulated by Lipopolysaccharide. Ricciardi-Castagnoli P (编). Dendritic Cells in Fundamental and Clinical Immunology. Advances in Experimental Medicine and Biology 417. Boston, MA: Springer US. 1997: 145–159. ISBN 978-1-4757-9968-2. PMID 9286353. doi:10.1007/978-1-4757-9966-8_25.
- ^ Sabroe I, Jones EC, Usher LR, Whyte MK, Dower SK. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses. Journal of Immunology. May 2002, 168 (9): 4701–4710. PMID 11971020. doi:10.4049/jimmunol.168.9.4701.
- ^ Yang H, Wang H, Ju Z, Ragab AA, Lundbäck P, Long W, Valdes-Ferrer SI, He M, Pribis JP, Li J, Lu B, Gero D, Szabo C, Antoine DJ, Harris HE, Golenbock DT, Meng J, Roth J, Chavan SS, Andersson U, Billiar TR, Tracey KJ, Al-Abed Y. MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. The Journal of Experimental Medicine. January 2015, 212 (1): 5–14. PMC 4291531 . PMID 25559892. doi:10.1084/jem.20141318.
- ^ Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA, Homer RJ, Goldstein DR, Bucala R, Lee PJ, Medzhitov R, Noble PW. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Medicine. November 2005, 11 (11): 1173–1179. PMID 16244651. S2CID 11765495. doi:10.1038/nm1315.
- ^ Fang H, Ang B, Xu X, Huang X, Wu Y, Sun Y, Wang W, Li N, Cao X, Wan T. TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells. Cellular & Molecular Immunology. March 2014, 11 (2): 150–159. PMC 4003380 . PMID 24362470. doi:10.1038/cmi.2013.59.
- ^ Hernandez C, Huebener P, Schwabe RF. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene. November 2016, 35 (46): 5931–5941. PMC 5119456 . PMID 27086930. doi:10.1038/onc.2016.104.
- ^ Jang GY, Lee JW, Kim YS, Lee SE, Han HD, Hong KJ, Kang TH, Park YM. Interactions between tumor-derived proteins and Toll-like receptors. Experimental & Molecular Medicine. December 2020, 52 (12): 1926–1935. PMC 8080774 . PMID 33299138. doi:10.1038/s12276-020-00540-4.
外部链接
- 醫學主題詞表（MeSH）：Toll-Like+Receptor+4
- PDB中UniProt可用的所有結構信息之概述：O00206 (Toll-like receptor 4) 在PDBe-KB。