Summary of TLR4

Toll-like receptors play a role in recognizing pathogens and activating the innate immune response [R]. The TLR4 protein recognizes LPS (lipopolysaccharide, a component of gram-negative bacteria), as well as viral and internal proteins [R, R2, R3].


The Function of TLR4

Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific (PubMed:20711192). Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303). In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (PubMed:23880187).

Protein names

Recommended name:

Toll-like receptor 4

Alternative name(s):

hToll
CD antigen CD284

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Top Gene-Substance Interactions

TLR4 Interacts with These Diseases

Fixes

Substances That Increase TLR4

Substances That Decrease TLR4

Advanced Summary

Conditions with Increased Gene Activity

Conditions with Decreased Gene Activity

Technical