TLR4

Het TLR4 gen bij mensen codeert de Toll-like receptor 4.^[1]^[2] Het detecteert lipopolysacchariden op de buitenmembraan van gram-negatieve bacteriën en is belangrijk voor het activeren van het aangeboren immuunsysteem. TLR4 wordt ook aangeduid met CD284 (cluster of differentiation 284).

Het door dit gen gecodeerde proteïne behoort tot de Toll-like receptor (TLR) familie, dat een fundamentele rol speelt in het herkennen van een ziekteverwekker en het activeren van het aangeboren immuunsysteem. Deze receptor komt het meeste tot expressie in de placenta en in de myelomonocytische subpopulatie van de leukocyten. Het is betrokken bij het doorgeven van signalen opgewekt door lipopolysacchariden (LPS) van gram-negatieve bacteriën. Mutaties van dit gen geven verschillen in reactie op LPS. Ook zijn er verscheiden transcriptie varianten van dit gen gevonden.^[3]

Interacties[bewerken | brontekst bewerken]

TLR 4 werkt samen met TOLLIP (Toll interacting protein),^[4] Myd88^[5]^[6]^[7]^[8] en lymfocyt antigeen 96.^[9]^[10]

Antagonistisch geneesmiddel[bewerken | brontekst bewerken]

Het lipide-A analoge eritoran reageert als een TLR4 antagonist en is een geneesmiddel tegen ernstige sepsis.^[11]

Externe link[bewerken | brontekst bewerken]

Toll-Like receptor 4

Bronnen, noten en/of referenties

↑ Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (Feb 1998). A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A 95 (2): 588–93. PMID 9435236. PMC 18464.
↑ Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (Aug 1997). A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388 (6640): 394–7. PMID 9237759. DOI: 10.1038/41131.
↑ Entrez Gene: TLR4 toll-like receptor 4. Gearchiveerd op 7 maart 2010.
↑ Zhang, Guolong, Ghosh Sankar (Mar. 2002). Negative regulation of toll-like receptor-mediated signaling by Tollip. J. Biol. Chem. 277 (9): 7059–65 (United States). ISSN: 0021-9258. PMID 11751856. DOI: 10.1074/jbc.M109537200.
↑ Chuang, Tsung-Hsien, Ulevitch Richard J (May. 2004). Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. 5 (5): 495–502 (United States). ISSN: 1529-2908. PMID 15107846. DOI: 10.1038/ni1066.
↑ Doyle, Sean E, O'Connell Ryan, Vaidya Sagar A, Chow Edward K, Yee Kathleen, Cheng Genhong (Apr. 2003). Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4. J. Immunol. 170 (7): 3565–71 (United States). ISSN: 0022-1767. PMID 12646618.
↑ Rhee, S H, Hwang D (Nov. 2000). Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase. J. Biol. Chem. 275 (44): 34035–40 (UNITED STATES). ISSN: 0021-9258. PMID 10952994. DOI: 10.1074/jbc.M007386200.
↑ Fitzgerald, K A, Palsson-McDermott E M, Bowie A G, Jefferies C A, Mansell A S, Brady G, Brint E, Dunne A, Gray P, Harte M T, McMurray D, Smith D E, Sims J E, Bird T A, O'Neill L A (Sep. 2001). Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413 (6851): 78–83 (England). ISSN: 0028-0836. PMID 11544529. DOI: 10.1038/35092578.
↑ Re, Fabio, Strominger Jack L (Jun. 2002). Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. J. Biol. Chem. 277 (26): 23427–32 (United States). ISSN: 0021-9258. PMID 11976338. DOI: 10.1074/jbc.M202554200.
↑ Shimazu, R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M (Jun. 1999). MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189 (11): 1777–82 (UNITED STATES). ISSN: 0022-1007. PMID 10359581.
↑ Tidswell, M, Tillis, W, Larosa, SP, Lynn, M, Wittek, AE (2010). Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis. Critical care medicine 38 (1): 72–83. PMID 19661804. DOI: 10.1097/CCM.0b013e3181b07b78.

[pmid9435236-1] Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (Feb 1998). A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A 95 (2): 588–93. PMID 9435236. PMC 18464.

[pmid9237759-2] Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (Aug 1997). A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388 (6640): 394–7. PMID 9237759. DOI: 10.1038/41131.

[3] Entrez Gene: TLR4 toll-like receptor 4. Gearchiveerd op 7 maart 2010.

[pmid11751856-4] Zhang, Guolong, Ghosh Sankar (Mar. 2002). Negative regulation of toll-like receptor-mediated signaling by Tollip. J. Biol. Chem. 277 (9): 7059–65 (United States). ISSN: 0021-9258. PMID 11751856. DOI: 10.1074/jbc.M109537200.

[pmid15107846-5] Chuang, Tsung-Hsien, Ulevitch Richard J (May. 2004). Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. 5 (5): 495–502 (United States). ISSN: 1529-2908. PMID 15107846. DOI: 10.1038/ni1066.

[pmid12646618-6] Doyle, Sean E, O'Connell Ryan, Vaidya Sagar A, Chow Edward K, Yee Kathleen, Cheng Genhong (Apr. 2003). Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4. J. Immunol. 170 (7): 3565–71 (United States). ISSN: 0022-1767. PMID 12646618.

[pmid10952994-7] Rhee, S H, Hwang D (Nov. 2000). Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase. J. Biol. Chem. 275 (44): 34035–40 (UNITED STATES). ISSN: 0021-9258. PMID 10952994. DOI: 10.1074/jbc.M007386200.

[pmid11544529-8] Fitzgerald, K A, Palsson-McDermott E M, Bowie A G, Jefferies C A, Mansell A S, Brady G, Brint E, Dunne A, Gray P, Harte M T, McMurray D, Smith D E, Sims J E, Bird T A, O'Neill L A (Sep. 2001). Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413 (6851): 78–83 (England). ISSN: 0028-0836. PMID 11544529. DOI: 10.1038/35092578.

[pmid11976338-9] Re, Fabio, Strominger Jack L (Jun. 2002). Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. J. Biol. Chem. 277 (26): 23427–32 (United States). ISSN: 0021-9258. PMID 11976338. DOI: 10.1074/jbc.M202554200.

[pmid10359581-10] Shimazu, R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M (Jun. 1999). MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189 (11): 1777–82 (UNITED STATES). ISSN: 0022-1007. PMID 10359581.

[11] Tidswell, M, Tillis, W, Larosa, SP, Lynn, M, Wittek, AE (2010). Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis. Critical care medicine 38 (1): 72–83. PMID 19661804. DOI: 10.1097/CCM.0b013e3181b07b78.

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