TLR4
Toll樣受體4（英語：Toll-like receptor 4, 縮寫：TLR4），也被稱為CD284（分化簇284，cluster of differentiation 284），是先天免疫反應的關鍵活化因子，在抵抗細菌感染中發揮着核心作用。TLR4是一種跨膜蛋白，分子量約為95 kDa，由TLR4基因編碼。
TLR4屬於Toll樣受體（TLR）家族，該家族是模式識別受體 (PRR) 中的代表。PRR之所以得名，是因為它們能夠識別微生物（細菌、病毒、真菌和寄生蟲）進化上保守的成分，即病原相關分子模式 (PAMP)。PRR識別PAMP後，會迅速活化先天免疫，這對於抵抗傳染病至關重要。[5]
TLR4主要在髓系來源的免疫細胞中表達，包括單核白血球、巨噬細胞和樹狀細胞（DC）[5]。它也在一些非免疫細胞上低水平表達，例如上皮細胞、內皮細胞、胎盤細胞和胰島β細胞。大多數髓系細胞還表達大量的質膜錨定CD14，CD14促進脂多糖（LPS）活化TLR4，並控制脂多糖活化的TLR4的後續內吞作用，這對於受體信號傳導和降解至關重要[6][7]。
TLR4的主要配體是脂多糖（LPS），它是革蘭氏陰性菌和某些革蘭氏陽性菌外膜的主要成分。TLR4也可被稱為損傷相關分子模式 (DAMP) 的內源性化合物活化，包括高遷移率族蛋白1 (HMGB1)、S100蛋白或組蛋白。這些化合物在組織損傷期間以及細胞死亡或壞死時釋放。[8][9][10][11][12]
TLR4是模式識別受體中Toll樣受體（TLR）家族的成員，可結合其配體脂多糖（LPS）活化NF-κB信號通路，在先天免疫系統中起到重要作用[5]。
參考文獻
[編輯]- ^ 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 (編). 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.
外部連結
[編輯]- 醫學主題詞表（MeSH）：Toll-Like+Receptor+4
- PDB中UniProt可用的所有結構資訊之概述：O00206 (Toll-like receptor 4) 在PDBe-KB。