TLR4

Toll-like receptor 4TLR 4TLR-4CD284TIRToll Like Receptor 4toll-like receptor (TLR) 4
Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene.wikipedia
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Toll-like receptor

Toll-like receptorsTLRToll
TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family.
The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the last three are not found in humans.

Pattern recognition receptor

pattern recognition receptorspattern recognition receptors (PRRs)(PRRs)
TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family.
TLRs tend to dimerize, TLR4 forms homodimers, and TLR6 can dimerize with either TLR1 or TLR2.

Lipopolysaccharide

endotoxinLPSlipopolysaccharides
It is most well-known for recognizing lipopolysaccharide (LPS), a component present in many Gram-negative bacteria (e.g. Neisseria spp.) and select Gram-positive bacteria. It cooperates with LY96 (also referred as MD-2) and CD14 to mediate in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria.
LPS acts as the prototypical endotoxin because it binds the CD14/TLR4/MD2 receptor complex in many cell types, but especially in monocytes, dendritic cells, macrophages and B cells, which promotes the secretion of pro-inflammatory cytokines, nitric oxide, and eicosanoids.

Pathogen-associated molecular pattern

PAMPspathogen-associated molecular patternsPAMP
They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity.
LPSs are specifically recognised by TLR4, a recognition receptor of the innate immune system.

CD14

CD14+antigens, cd14CD14+ cells
It cooperates with LY96 (also referred as MD-2) and CD14 to mediate in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria.
CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS).

TRIF

This TRIF-dependent pathway involves the recruitment of the adaptor proteins TIR-domain-containing adaptor inducing interferon-β (TRIF) and TRIF-related Adaptor Molecule (TRAM).
Curiously, there is a lack of redundancy within the TLR4 signaling pathway that leads to microbial evasion of immune response in the host after mutations occur within intermediates of the pathway.

MYD88

The MyD88-dependent pathway is regulated by two adaptor-associated proteins: Myeloid Differentiation Primary Response Gene 88 (MyD88) and TIR Domain-Containing Adaptor Protein (TIRAP).
Mal (also known as TIRAP) is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88 then signals through IRAK.

RAB11A

RAB11Rab-11A
Intracellular trafficking of TLR4 is dependent on the GTPase Rab-11a, and knock down of Rab-11a results in hampered TLR4 recruitment to ''E.
Rab-11a controls intracellular trafficking of the innate immune receptor TLR4, and thereby also receptor signalling

Lymphocyte antigen 96

MD-2LY96MD-2 (immunology)
It cooperates with LY96 (also referred as MD-2) and CD14 to mediate in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria.
The protein encoded by this gene is involved in binding lipopolysaccharide with TLR4.

Toll-Interleukin receptor

Toll/IL-1 receptor (TIR)toll/interleukin-1 receptortoll/interleukin-1 receptor (TIR) domain
TLR4 signaling responds to signals by forming a complex using an extracellular leucine-rich repeat domain (LRR) and an intracellular toll/interleukin-1 receptor (TIR) domain.
MYD88; SIGIRR; TLR1; TLR10; TLR2; TLR3; TLR4; TLR5;

Lipopolysaccharide binding protein

Lipopolysaccharide-binding proteinLBPLBP protein
LPS recognition is initiated by an LPS binding to an LBP protein.
Lipopolysaccharide-binding protein has been shown to interact with CD14, TLR2, TLR4 and the co-receptor MD-2.

Opioid

opioidsopioid-induced constipationopioid analgesic
Toll-like receptor 4 has been shown to be important for the long-term side-effects of opioid analgesic drugs.
This appears to largely be a result of actions of opioid drugs at targets other than the three classic opioid receptors, including the nociceptin receptor, sigma receptor and Toll-like receptor 4, and can be counteracted in animal models by antagonists at these targets such as J-113,397, BD-1047 or -naloxone respectively.

Fetuin

Fetuin-A
Fetuin-A facilitates the binding of lipids to receptors, thereby inducing insulin resistance.
Fetuin-A has been shown to facilitate the binding of free fatty acids to TLR4 receptors, thereby inducing insulin resistance in mice.

TOLLIP

TOLLIP has been shown to interact with TOM1, TLR 2, TLR 4 and IL1RAP.

Morphine

morphiamorphine addictionmorphine sulfate
Various μ-opioid receptor ligands have been tested and found to also possess action as agonists or antagonists of TLR4, with opioid agonists such as morphine being TLR4 agonists, while opioid antagonists such as naloxone were found to be TLR4 antagonists.
Usually, the p38 within the dendritic cell expresses TLR 4 (toll-like receptor 4), which is activated through the ligand LPS (lipopolysaccharide).

(+)-Naloxone

* -naloxone ("unnatural" isomer, lacks opioid receptor affinity so selective for TLR4 inhibition)
Unlike "normal" naloxone, -naloxone has no significant affinity for opioid receptors, but instead has been discovered to act as a selective antagonist of Toll-like receptor 4.

Buprenorphine

SubutexSuboxoneProbuphine
Similarly to various other opioids, buprenorphine has also been found to act as an agonist of the toll-like receptor 4, albeit with very low affinity.

Eritoran

eritoran tetrasodium
* The lipid A analog eritoran acts as a TLR4 antagonist.
Toll-like receptor 4 (TLR4) detects lipopolysaccharides found in most Gram-negative bacteria.

Lipid A

* The lipid A analog eritoran acts as a TLR4 antagonist.
The biological activity of LPS depends on the chemical structure of its lipid A. Primarily, TLR4 is required for activation of innate immunity upon recognition of LPS of Gram-negative bacteria.

Ibudilast

Ibudilast is principally a PDE4 inhibitor but has also been shown to act as an antagonist at the toll-like receptor 4 (TLR4).

Protein

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

Gene

genesnumber of genesgene sequence
Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene.

NF-κB

NF-kBNF-kappaBNFκB
Its activation leads to an intracellular signaling pathway NF-κB and inflammatory cytokine production which is responsible for activating the innate immune system.

Gram-negative bacteria

Gram-negativeGram negativeGram-negative bacterium
It is most well-known for recognizing lipopolysaccharide (LPS), a component present in many Gram-negative bacteria (e.g. Neisseria spp.) and select Gram-positive bacteria. It cooperates with LY96 (also referred as MD-2) and CD14 to mediate in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria.

Gram-positive bacteria

Gram-positiveGram positivegram-positive bacterium
It is most well-known for recognizing lipopolysaccharide (LPS), a component present in many Gram-negative bacteria (e.g. Neisseria spp.) and select Gram-positive bacteria.