Original Literature | Model OverView |
---|---|
Publication
Title
Innate immunity and toll-like receptors: clinical implications of basic scienceresearch.
Affiliation
Inflammatory Bowel Disease Center, Division of Gastroenterology, Department ofMedicine, Steven Spielberg Pediatric Research Center, Los Angeles, CA 90048,USA.
Abstract
Humans are constantly exposed to a wide variety of microorganisms that can causeinfection. In self-defense, the human host has evolved complex protectivemechanisms, and Toll-like receptors (TLRs) have emerged as a central point indefense. These receptors bind molecular structures that are expressed bymicrobes but are not expressed by the human host, eg, lipopolysaccharides (LPS)or double-stranded RNA (dsRNA). Activation of these receptors initiates aninflammatory cascade that attempts to clear the offending pathogen and set inmotion a specific adaptive immune response. Defects in sensing of pathogens maypredispose the host to recurrent infections. The relative rarity of thesesyndromes of defective innate immunity, however, speaks to the redundancy insensing of pathogens by the innate immune system. More common, polymorphisms inTLR4 are associated with increased predisposition to severe and recurrentinfections but protection against atherosclerotic disease due to diminishedinflammation. Toll-like receptor signaling may also contribute to thepathophysiology of disease and injure the host by activating a deleteriousimmune response such as in sepsis or inflammatory bowel disease (IBD). The focusof this article is to describe the role of TLRs in the innate immune response inhealth and disease.
PMID
15069387
|
Entity
NF-kappaB
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m15
10
infinite
0
TRANSPATH | MO000000058 |
--
TLR4
--
MO000019394
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3961
10
infinite
0
InterPro | IPR000157 |
TRANSPATH | MO000019394 |
--
TLR2
--
MO000019397
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3964
10
infinite
0
InterPro | IPR000157 |
TRANSPATH | MO000019397 |
--
dsRNA:TLR3
--
MO000041446
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m19314
10
infinite
0
TRANSPATH | MO000041446 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m1
0
infinite
0
--
--
e10
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytosol
--
--
--
csml-variable:Double
m10
0
infinite
0
--
LPS:MD-2:TLR4: MyD88: MAL: TIRAP
--
e11
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m11
0
infinite
0
--
MAL
--
e12
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m12
0
infinite
0
--
LPS:MD-2:TLR4: MyD88: MAL: TIRAP: IRAK
--
e13
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m13
0
infinite
0
--
IkappaB {actiavted}
--
e14
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m14
10
infinite
0
TRANSPATH | MO000000215 |
--
NF-kappaB {activated}
--
e15
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m16
10
infinite
0
TRANSPATH | MO000000058 |
--
NF-kappaB {nucleus}
--
e16
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m17
10
infinite
0
TRANSPATH | MO000000058 |
--
csml-variable:Double
m18
10
infinite
0
Affymetrix | 1520_s_at |
Ensembl | ENSG00000125538 |
HGNC | IL1B |
OMIM | 137215 |
Proteome | HumanPSD/IL1B |
RefSeq | NM_000576 |
TRANSFAC | G000311 |
Unigene | Hs.126256 |
--
IL-8
--
e18
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m19
0
infinite
0
--
TLR1: TLR2
--
e19
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m20
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
TLR6:TLR2
--
e20
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m21
0
infinite
0
--
PGN: TLR2
--
e21
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m22
0
infinite
0
--
lipopeptide: TLR6:TLR2
--
e22
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m23
0
infinite
0
--
lipopeptides: TLR1: TLR2
--
e23
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m24
0
infinite
0
--
csml-variable:Double
m25
0
infinite
0
--
LPS: TLR2
--
e25
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m26
0
infinite
0
--
flagellin: TLR5
--
e26
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m27
0
infinite
0
--
type I IFN
--
e29
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m30
0
infinite
0
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
RSV F: CD14
--
e30
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m31
0
infinite
0
--
RSV F
--
e31
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m32
0
infinite
0
--
RSV F: CD14: TLR4
--
e32
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m33
0
infinite
0
--
csml-variable:Double
m34
0
infinite
0
--
CpG DNA: TLR9
--
e34
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m35
0
infinite
0
--
Ligand: TLR
--
e35
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m36
0
infinite
0
--
pneumolysin
--
e36
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m37
0
infinite
0
--
pneumolysin: TLR4
--
e37
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m38
0
infinite
0
--
csml-variable:Double
m39
0
infinite
0
--
TGF-beta
--
e39
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m40
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
TGF-beta
--
e41
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m42
0
infinite
0
--
IFN-beta
--
e42
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m43
0
infinite
0
--
LPS:MD-2
--
e5
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m5
0
infinite
0
--
--
e50
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelopeLumen
--
--
--
csml-variable:Double
m50
0
infinite
0
--
--
e51
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearPore
--
--
--
csml-variable:Double
m51
0
infinite
0
--
--
e52
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearInnerMembrane
--
--
--
csml-variable:Double
m52
0
infinite
0
--
--
e53
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearLumen
--
--
--
csml-variable:Double
m53
0
infinite
0
--
--
e54
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearOuterMembrane
--
--
--
csml-variable:Double
m54
0
infinite
0
--
--
e55
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleus
--
--
--
csml-variable:Double
m55
0
infinite
0
--
--
e56
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
--
--
--
csml-variable:Double
m56
0
infinite
0
--
--
e57
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearBody
--
--
--
csml-variable:Double
m57
0
infinite
0
--
--
e58
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleolus
--
--
--
csml-variable:Double
m58
0
infinite
0
--
--
e59
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
--
--
--
csml-variable:Double
m59
0
infinite
0
--
LPS:MD-2:TLR4
--
e6
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m6
0
infinite
0
--
--
e60
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
--
--
--
csml-variable:Double
m60
0
infinite
0
--
--
e61
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearChromosome
--
--
--
csml-variable:Double
m61
0
infinite
0
--
--
e62
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
--
--
--
csml-variable:Double
m62
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
p1
p1
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
m155666*m6438*0.1
nodelay
--
0
PMID: 15069387, 11593030, 11500507 MD-2 is a secreted protein that may function by binding to LPS and to the extracellular domain of TLR4, where it facilitates LPS responsiveness.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c28 : 1
m17*0.1
nodelay
--
0
PMID: 15069387, 9237759 Interaction of LPS with its receptor TLR4 triggers a complex signaling pathway that leads to the activation of transcription actors, such as nuclear factor- jB (NF-jB), which then induce the activation of the inflammatory genes, such as tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, and IL-8.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1
m17*0.1
nodelay
--
0
PMID: 15069387, 9237759 Interaction of LPS with its receptor TLR4 triggers a complex signaling pathway that leads to the activation of transcription actors, such as nuclear factor- jB (NF-jB), which then induce the activation of the inflammatory genes, such as tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, and IL-8.
p12
p12
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c32 : 1
stoichiometry:c33 : 1
m3964*m3963*0.1
nodelay
--
0
PMID: 15069387 Toll-like receptor 2, in combination with TLR6 or TLR1, mediates responses to multiple other microbial pathogens.
p13
p13
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c35 : 1
stoichiometry:c36 : 1
m3987*m3964*0.1
nodelay
--
0
PMID: 15069387 Toll-like receptor 2, in combination with TLR6 or TLR1, mediates responses to multiple other microbial pathogens.
p14
p14
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c38 : 1
stoichiometry:c39 : 1
m3964*m155701*0.1
nodelay
--
0
PMID: 15069387, 10384090 Pathogen-associated molecular patterns of gram-positive organisms, such as peptidoglycan and lipopeptides, are recognized by TLR2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c43 : 1
stoichiometry:c44 : 1
m25*m20*0.1
nodelay
--
0
PMID: 15069387, 10384090 Pathogen-associated molecular patterns of gram-positive organisms, such as peptidoglycan and lipopeptides, are recognized by TLR2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c45 : 1
m25*m21*0.1
nodelay
--
0
PMID: 15069387, 10384090 Pathogen-associated molecular patterns of gram-positive organisms, such as peptidoglycan and lipopeptides, are recognized by TLR2.
p17
p17
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c47 : 1
stoichiometry:c48 : 1
m155666*m3964*0.1
nodelay
--
0
PMID: 15069387, 10816537 LPS from Leptospira interogans30 and Porphyromonas gingivalis (periodontal disease) activates macrophages through TLR2.
p18
p18
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c50 : 1
stoichiometry:c51 : 1
m6485*m3966*0.1
nodelay
--
0
PMID: 15069387, 11323673 Toll-like receptor 5 has been found to be the receptor for monomeric flagellin.
p19
p19
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c53 : 1
stoichiometry:c54 : 1
m1055*m119368*0.1
nodelay
--
0
PMID: 15069387, 7568028 dsRNA is known to bind only intracellular targets, including the dsRNA-dependent protein kinase (PKR).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1
m5*m3961*0.1
nodelay
--
0
PMID: 15069387, 11593030, 11500507 MD-2 is a secreted protein that may function by binding to LPS and to the extracellular domain of TLR4, where it facilitates LPS responsiveness.
p20
p20
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c56 : 1
stoichiometry:c57 : 1
m119368*m3965*0.1
nodelay
--
0
PMID: 15069387, 11607032, 12646618 Studies have shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces NF-kappaB and the production of type I IFNs.
p21
p21
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c60 : 1
stoichiometry:c59 : 1
m15*m19314*0.1
nodelay
--
0
PMID: 15069387, 11607032, 12646618 Studies have shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces NF-kappaB and the production of type I IFNs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c62 : 1
m19314*0.1
nodelay
--
0
PMID: 15069387, 11607032, 12646618 Studies have shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces NF-kappaB and the production of type I IFNs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c64 : 1
m29*0.1
nodelay
--
0
PMID: 15069387, 11607032, 12646618 Studies have shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces NF-kappaB and the production of type I IFNs.
p24
p24
cso30:i:ME_Binding
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c65 : 1
stoichiometry:c66 : 1
stoichiometry:c67 : 1
m2828*m32*0.1
nodelay
--
0
PMID: 15069387, 11062499 The innate immune response to fusion protein F of respiratory syncytial virus (RSV) is mediated by TLR4 and CD14.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
stoichiometry:c70 : 1
m3961*m31*0.1
nodelay
--
0
PMID: 15069387, 11062499 The innate immune response to fusion protein F of respiratory syncytial virus (RSV) is mediated by TLR4 and CD14.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c75 : 1
stoichiometry:c73 : 1
m34*m19828*0.1
nodelay
--
0
PMID: 15069387, 11470918 Toll-like receptor 9 has been shown to be the receptor for CpG DNA.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c76 : 1
m36*0.1
nodelay
--
0
PMID: 15069387, 9237759 Pathogen-associated molecular pattern recognition by TLRs in macrophages and antigen-presenting cells also leads to the expression of costimulatory molecules such as CD80 (B7.1) and CD86 (B7.2), which bind to CD28 on T lymphocytes to assist in antigen presentation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c77 : 1
m36*0.1
nodelay
--
0
PMID: 15069387, 9237759 Pathogen-associated molecular pattern recognition by TLRs in macrophages and antigen-presenting cells also leads to the expression of costimulatory molecules such as CD80 (B7.1) and CD86 (B7.2), which bind to CD28 on T lymphocytes to assist in antigen presentation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c80 : 1
m95018*0.1
nodelay
--
0
PMID: 15069387, 9237759 Pathogen-associated molecular pattern recognition by TLRs in macrophages and antigen-presenting cells also leads to the expression of costimulatory molecules such as CD80 (B7.1) and CD86 (B7.2), which bind to CD28 on T lymphocytes to assist in antigen presentation.
p3
p3
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1
stoichiometry:c11 : 1
stoichiometry:c10 : 1
m6*m1572*m12*m6810*0.1
nodelay
--
0
PMID: 15069387 The adapter proteins MyD88 and TIRAP/MAL associate via TIRmediated interactions with the TLR, and initiate the formation of a signaling complex involving interleukinreceptor?associated kinases (IRAKs).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c81 : 1
m93745*0.1
nodelay
--
0
PMID: 15069387, 9237759 Pathogen-associated molecular pattern recognition by TLRs in macrophages and antigen-presenting cells also leads to the expression of costimulatory molecules such as CD80 (B7.1) and CD86 (B7.2), which bind to CD28 on T lymphocytes to assist in antigen presentation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c82 : 1
m35*0.1
nodelay
--
0
PMID: 15069387 LPS- or CpGactivated dendritic cells produce IL-6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c85 : 1
stoichiometry:c86 : 1
m3961*m37*0.1
nodelay
--
0
PMID: 15069387, 12569171 a recent study found that pneumolysin, a pneumococcal virulence factor, is recognized by TLR4 and that this recognition confers resistance to pneumococcal infection.
p33
p33
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c88 : 1
stoichiometry:c89 : 1
stoichiometry:c90 : 1
m2126*m387*m2125*0.1
nodelay
--
0
PMID: 15069387, 9237759 Pathogen-associated molecular pattern recognition by TLRs in macrophages and antigen-presenting cells also leads to the expression of costimulatory molecules such as CD80 (B7.1) and CD86 (B7.2), which bind to CD28 on T lymphocytes to assist in antigen presentation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c92 : 1
m36*0.1
nodelay
--
0
PMID: 15069387 Dendritic cell production of IL-12 shifts Th0 development towards Th1 differentiation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
m36*0.1
nodelay
--
0
PMID: 15069387 Dendritic cell production of IL-12 shifts Th0 development towards Th1 differentiation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c98 : 1
m41*0.1
nodelay
--
0
PMID: 15069387 Dendritic cell production of IL-12 shifts Th0 development towards Th1 differentiation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c97 : 1
m40*0.1
nodelay
--
0
PMID: 15069387 Dendritic cell production of IL-12 shifts Th0 development towards Th1 differentiation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c99 : 1
m26*0.1
nodelay
--
0
PMID: 15069387, 12646604 In vitro studies demonstrate that this polymorphism in TLR2 results in diminished TNF-a production in response toMtuberculosis andMleprae infection, providing a mechanistic explanation for the clinical findings.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c102 : 1
m93309*0.1
nodelay
--
0
12646604 In vitro studies demonstrate that this polymorphism in TLR2 results in diminished TNF-a production in response toMtuberculosis andMleprae infection, providing a mechanistic explanation for the clinical findings.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1
m11*m184*0.1
nodelay
--
0
PMID: 15069387 The adapter proteins MyD88 and TIRAP/MAL associate via TIRmediated interactions with the TLR, and initiate the formation of a signaling complex involving interleukinreceptor?associated kinases (IRAKs).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c103 : 1
stoichiometry:c104 : 1
m36*0.1
nodelay
--
0
PMID: 15069387 an alternative TLR-signaling pathway that leads to the production of the antiviral cytokine IFN-b has been reported in mice.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c105 : 1
m93217*0.1
nodelay
--
0
PMID: 15069387 an alternative TLR-signaling pathway that leads to the production of the antiviral cytokine IFN-b has been reported in mice.
p5
p5
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1
m13*m186*0.1
nodelay
--
0
PMID: 15069387 TLR4 triggers a complex signaling pathway that leads to the activation of transcription factors, such as nuclear factor- jB (NF-kappaB).
p6
p6
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c20 : 1
stoichiometry:c19 : 1
m15*m14*0.1
nodelay
--
0
PMID: 15069387 TLR4 triggers a complex signaling pathway that leads to the activation of transcription factors, such as nuclear factor- jB (NF-kappaB).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1
m16*0.1
nodelay
--
0
PMID: 15069387 Toll-like receptors share a common activation pathway mediated through their TIR signaling domains, resulting in the nuclear translocation and activation of the pro-inflammatory transcription factor NF-kappaB.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c23 : 1
m17*0.1
nodelay
--
0
PMID: 15069387, 9237759 Interaction of LPS with its receptor TLR4 triggers a complex signaling pathway that leads to the activation of transcription actors, such as nuclear factor- jB (NF-jB), which then induce the activation of the inflammatory genes, such as tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, and IL-8.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c24 : 1
m17*0.1
nodelay
--
0
PMID: 15069387, 9237759 Interaction of LPS with its receptor TLR4 triggers a complex signaling pathway that leads to the activation of transcription actors, such as nuclear factor- jB (NF-jB), which then induce the activation of the inflammatory genes, such as tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, and IL-8.
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--