Synonyms 类Toll受体4, ARMD10, CD284 + [5] |
Introduction Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634, PubMed:27022195, PubMed:21393102). 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). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor (PubMed:16622205, PubMed:10835634, PubMed:15809303, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:9237759). Activated by the signaling pathway regulator NMI which acts as damage-associated molecular patterns (DAMPs) in response to cell injury or pathogen invasion, therefore promoting nuclear factor NF-kappa-B activation (PubMed:29038465). |
Target |
Mechanism TLR4 antagonists |
Active Org. |
Originator Org. |
Active Indication |
Inactive Indication |
Drug Highest PhasePhase 3 |
First Approval Ctry. / Loc.- |
First Approval Date20 Jan 1800 |
Target |
Mechanism NGFB stimulants [+1] |
Active Org. |
Originator Org. |
Active Indication |
Inactive Indication |
Drug Highest PhasePhase 2 |
First Approval Ctry. / Loc.- |
First Approval Date20 Jan 1800 |
Target |
Mechanism TLR4 agonists |
Active Org. ![]() |
Originator Org. ![]() |
Active Indication |
Inactive Indication- |
Drug Highest PhasePhase 2 |
First Approval Ctry. / Loc.- |
First Approval Date20 Jan 1800 |
Start Date01 Dec 2023 |
Sponsor / Collaborator |
Start Date18 Oct 2023 |
Sponsor / Collaborator |
Start Date15 Sep 2023 |
Sponsor / Collaborator |