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Toll like receptor 4 (TLR4)

Toll like receptor 4 is a protein that in humans is encoded by the TLR4 gene.

TLR 4 is a toll-like receptor which is responsible for activating the innate immune system. It is most well-known for recognizing lipopolysaccharide (LPS), a component of Gram-negative bacteria, but its ligands also include several viral proteins, polysaccharide, and a variety of endogenous proteins such as low-density lipoprotein, beta-defensins, and heat shock protein.

TLR 4 has also been designated as CD284 (cluster of differentiation 284). The molecular weight of TLR 4 is approximately 95 kDa.

Tang et al. identify endothelial Toll-like receptor 4 (TLR4) and the gut microbiome as critical stimulants of cerebral cavernous malformation formation. Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or pharmacologic blockade of TLR4 signalling prevents CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ-free mice are protected from CCM formation, and a single course of antibiotics permanently alters CCM susceptibility in mice. These studies identify unexpected roles for the microbiome and innate immune signalling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment 1).

A single treatment of hyperbaric oxygen (HBO) therapy immediately after middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion significantly reduces edema and may improve perfusion. TLR4 knockout protects mice from MCAO damage, but to a lesser extent than HBO treatment 2).

Cerebral ischemia-reperfusion injury in rats can be alleviated via the inhibition of the TLR4/NF-κB signaling pathway 3).

Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N, Girard R, Zeineddine HA, Lightle R, Moore T, Cao Y, Shenkar R, Chen M, Mericko P, Yang J, Li L, Tanes C, Kobuley D, Võsa U, Whitehead KJ, Li DY, Franke L, Hart B, Schwaninger M, Henao-Mejia J, Morrison L, Kim H, Awad IA, Zheng X, Kahn ML. Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature. 2017 May 10. doi: 10.1038/nature22075. [Epub ahead of print] PubMed PMID: 28489816.
Pushkov D, Nicholson JD, Michowiz S, Novitzky I, Weiss S, Ben Hemou M, Hochhauser E, Goldenberg-Cohen N. Relative neuroprotective effects hyperbaric oxygen treatment and TLR4 knockout in a mouse model of temporary middle cerebral artery occlusion. Int J Neurosci. 2016 Feb;126(2):174-181. Epub 2015 May 22. PubMed PMID: 25562174.
Zhao H, Chen Z, Xie LJ, Liu GF. Suppression of TLR4/NF-κB Signaling Pathway Improves Cerebral Ischemia-Reperfusion Injury in Rats. Mol Neurobiol. 2017 Jun 17. doi: 10.1007/s12035-017-0552-0. [Epub ahead of print] PubMed PMID: 28624894.
tlr4.txt · Last modified: 2017/06/19 15:10 by administrador