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).

TLR4

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]

Toll-like receptoren van het aangeboren immuunsysteem herkent LPS en zorgt voor een immuunreactie.

Interacties

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

Antagonistisch geneesmiddel

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

Externe link

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.
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.
(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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[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.

[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] (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.