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PMID: 17275324 LBP is thought to be a shuttle protein catalyzing LPS transfer from the outer membrane of Gram-negative bacteria to CD14, another LPS binding molecule.

PMID: 17275324 LBP is thought to be a shuttle protein catalyzing LPS transfer from the outer membrane of Gram-negative bacteria to CD14, another LPS binding molecule.

indirect

PMID: 17275324 CD14 has a role in loading LPS to the receptor complex consisting of TLR4 and MD-2. PMID: 17275324,11150311 Recombinant EDA, but not other recombinant fibronectin domains, induces expression of a matrix methalloproteinase MMP-9 in human macrophages by stimulating TLR4

PMID: 17275324 LPS is similar to a cytokine in that it interacts with a receptor TLR4/MD-2, and induces oligomerization of TLR4, leading to activation of downstream signaling pathways by recruiting downstream adaptor molecules

PMID: 17275324,15557191,15010525,11521076 Direct interaction between LPS and purified MD-2 without TLR4 was also reported whereas the direct interaction between TLR4 and LPS has not been demonstrated.

PMID: 17275324 Figure 1 PMID: 17275324 ‘MyD88-dependent’ pathway, requires two adaptor molecules, myeloid differentiation factor 88 (MyD88) and MyD88 adapterlike (Mal)/TIR domain-containing protein (TIRAP), and leads to early activation of the transcription factor NF-KappaB, the production of proinflammatory cytokines, and Th1 responses.

indirect

PMID: 17275324 Figure 1 PMID: 17275324 ‘MyD88-dependent’ pathway, requires two adaptor molecules, myeloid differentiation factor 88 (MyD88) and MyD88 adapterlike (Mal)/TIR domain-containing protein (TIRAP), and leads to early activation of the transcription factor NF-KappaB, the production of proinflammatory cytokines, and Th1 responses.

indirect

indirect

PMID: 17275324 Figure 1 PMID: 17275324 ‘MyD88-dependent’ pathway, requires two adaptor molecules, myeloid differentiation factor 88 (MyD88) and MyD88 adapterlike (Mal)/TIR domain-containing protein (TIRAP), and leads to early activation of the transcription factor NF-kappaB, the production of proinflammatory cytokines, and Th1 responses.

PMID: 17275324 Figure 1 PMID: 17275324 A second set of adaptor molecules, TIR domain-containing adapter inducing interferon-beta (TRIF)/TIR domain-containing adapter molecule-1 (TICAM-1) and TRIF-related adapter molecule (TRAM)/TIR domain-containing adapter molecule- 2 (TICAM-2), are required for LPS-induced phosphorylation and dimerization of the transcription factor IRF-3, leading to interferon-beta (IFN-beta) production

indirect

PMID: 17275324 A second set of adaptor molecules, TIR domain-containing adapter inducing interferon-beta (TRIF)/TIR domain-containing adapter molecule-1 (TICAM-1) and TRIF-related adapter molecule (TRAM)/TIR domain-containing adapter molecule- 2 (TICAM-2), are required for LPS-induced phosphorylation and dimerization of the transcription factor IRF-3, leading to interferon-beta (IFN-beta) production

indirect

PMID: 17275324 A second set of adaptor molecules, TIR domain-containing adapter inducing interferon-beta (TRIF)/TIR domain-containing adapter molecule-1 (TICAM-1) and TRIF-related adapter molecule (TRAM)/TIR domain-containing adapter molecule- 2 (TICAM-2), are required for LPS-induced phosphorylation and dimerization of the transcription factor IRF-3, leading to interferon-beta (IFN-beta) production PMID: 17275324 Figure 1

indirect

indirect

PMID: 17275324 A second set of adaptor molecules, TIR domain-containing adapter inducing interferon-beta (TRIF)/TIR domain-containing adapter molecule-1 (TICAM-1) and TRIF-related adapter molecule (TRAM)/TIR domain-containing adapter molecule- 2 (TICAM-2), are required for LPS-induced phosphorylation and dimerization of the transcription factor IRF-3, leading to interferon-beta (IFN-beta) production PMID: 17275324 Figure 1

PMID: 17275324 Tricacylated lipopeptide is recognized by TLR1/TLR2, whereas diacylated lipopeptide is sensed by TLR2/TLR6.

PMID: 17275324,15895089,15690042 CD14 is required for diacylated lipopeptides and lipoteichoic acid whereas forward genetics revealed thatCD36 is another accessory molecule for TLR2 in its response to diacylated lipopeptide and lipoteichoic acid

PMID: 17275324,15895089,15690042 CD14 is required for diacylated lipopeptides and lipoteichoic acid whereas forward genetics revealed thatCD36 is another accessory molecule for TLR2 in its response to diacylated lipopeptide and lipoteichoic acid

PMID: 17275324,15895089,15690042 CD14 is required for diacylated lipopeptides and lipoteichoic acid whereas forward genetics revealed thatCD36 is another accessory molecule for TLR2 in its response to diacylated lipopeptide and lipoteichoic acid

PMID: 17275324,15895089,15690042 CD14 is required for diacylated lipopeptides and lipoteichoic acid whereas forward genetics revealed thatCD36 is another accessory molecule for TLR2 in its response to diacylated lipopeptide and lipoteichoic acid

PMID: 17275324,15895089,15690042 CD14 is required for diacylated lipopeptides and lipoteichoic acid whereas forward genetics revealed thatCD36 is another accessory molecule for TLR2 in its response to diacylated lipopeptide and lipoteichoic acid

PMID: 17275324,15895089,15690042 CD14 is required for diacylated lipopeptides and lipoteichoic acid whereas forward genetics revealed thatCD36 is another accessory molecule for TLR2 in its response to diacylated lipopeptide and lipoteichoic acid

PMID: 17275324 A/D-type CpG is retained for long periods in the endosomal vesicles of plasmacytoid dendritic cells, together with the complex consisting of downstream signaling molecules, whereas the B/K-type CpG. is recognized by TLR9 in the lysosome.

PMID: 17275324 A/D-type CpG is retained for long periods in the endosomal vesicles of plasmacytoid dendritic cells, together with the complex consisting of downstream signaling molecules, whereas the B/K-type CpG. is recognized by TLR9 in the lysosome.

indirect

PMID: 17275324 The LPS coreceptor MD-2 was also shown to facilitate glycosylation and cell surface expression of TLR4.

PMID: 17275324,7897216 Radioprotective 105 (RP105) is most similar to TLR4 in extracellular leucine-rich repeats than other members of the Toll family, and forms a complex with MD-1, cloning of which led to the cloning of MD-2 as a molecule similar to MD-1

PMID: 17275324,15852007 A molecular mechanism by which RP105/MD-1 contribute to B cell responses to TLR4/MD-2 and TLR2 ligands was suggested by a recent report demonstrating that RP105/MD-1 is associated with TLR4/MD-2

indirect

indirect

indirect

PMID: 17275324,10623794,11402040 HSP60-dependent induction of TNF-alpha and NO in macrophages was dependent on TLR4 signaling

indirect

indirect

indirect

PMID: 17275324,10623794,11402040 HSP60-dependent induction of TNF-alpha and NO in macrophages was dependent on TLR4 signaling

indirect

PMID: 17275324,11842086 HSP70 induces interleukin-12 (IL-12) production in macrophages

indirect

indirect

PMID: 17275324,11912201 An ER chaperone gp96 induces production of proinflammatory cytokines and upregulation of co-stimulatory molecules in bone marrow DCs from wild type mice, whereas DCs from TLR4 mutant or TLR4/TLR2 double mutant mice failed to respond to gp96

indirect

PMID: 17275324,11912201 An ER chaperone gp96 induces production of proinflammatory cytokines and upregulation of co-stimulatory molecules in bone marrow DCs from wild type mice, whereas DCs from TLR4 mutant or TLR4/TLR2 double mutant mice failed to respond to gp96

PMID: 17275324 An ER chaperon gp96 is associated with TLR4 in ER and required for cell surface expression of TLR4

indirect

indirect

PMID: 17275324 An ER chaperon gp96 is associated with TLR4 in ER and required for cell surface expression of TLR4

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

PMID: 17275324 Biglycan, a small leucine-rich proteoglycan in ECM component, acts on macrophages as an endogenous ligand of TLR4 and TLR2, leading to rapid activation of p38, ERK, and NF-KappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2).

indirect

indirect

indirect

indirect

indirect

indirect

PMID: 17275324 Moreover, biglycan was shown to be physically associated with CD14/TLR4/MD-2.

indirect

PMID: 17275324,11150311 Recombinant EDA, but not other recombinant fibronectin domains, induces expression of a matrix methalloproteinase MMP-9 in human macrophages by stimulating TLR4

PMID: 17275324 CD14 has a role in loading LPS to the receptor complex consisting of TLR4 and MD-2. PMID: 17275324,12055204 SP-A induces NF-KappaB activation and cytokine production such as TNF-alpha and IL-10 in macrophages by stimulating TLR4

indirect

PMID: 17275324,12055204 SP-A induces NF-KappaB activation and cytokine production such as TNF-alpha and IL-10 in macrophages by stimulating TLR4

indirect

indirect

PMID: 17275324,12055204 SP-A induces NF-KappaB activation and cytokine production such as TNF-alpha and IL-10 in macrophages by stimulating TLR4

indirect

indirect

PMID: 17275324,12055204 SP-A induces NF-KappaB activation and cytokine production such as TNF-alpha and IL-10 in macrophages by stimulating TLR4

PMID: 17275324,15795240 High-mobility group box 1 (HMGB1) was identified as an endogenous ligand for TLR4/MD-2 and TLR2 that serves as a late mediator of lethality in sepsis and as an early mediator of inflammation and organ damage in hepatic ischemia reperfusion injury, a pathophysiologic process whereby hypoxic organ damage is accentuated following return of blood flow and oxygen delivery

PMID: 17275324,15795240 High-mobility group box 1 (HMGB1) was identified as an endogenous ligand for TLR4/MD-2 and TLR2 that serves as a late mediator of lethality in sepsis and as an early mediator of inflammation and organ damage in hepatic ischemia reperfusion injury, a pathophysiologic process whereby hypoxic organ damage is accentuated following return of blood flow and oxygen delivery

indirect

indirect

PMID: 17275324 Oxidized low-density lipoprotein (OxLDL) induces actin polymerization and spreading of macrophages, which results in pro-atherogenic consequences as inhibition of phagocytosis of apoptotic cells but enhancement of OxLDL uptake. PMID: 17275324,12424240 This effect is mediated by TLR4/MD-2 but not by TLR2

PMID: 17275324,12411706 Beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. Murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for TLR4, inducing upregulation of co-stimulatory molecules and dendritic cell maturation

indirect

PMID: 17275324,12411706 Beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. Murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for TLR4, inducing upregulation of co-stimulatory molecules and dendritic cell maturation