Entity
csml-variable:Double
m1
0
infinite
0
--
csml-variable:Double
m10
0
infinite
0
--
csml-variable:Double
m11
0
infinite
0
--
IL-18{inactive}
--
e12
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m12
0
infinite
0
--
csml-variable:Double
m13
0
infinite
0
--
csml-variable:Double
m14
0
infinite
0
--
caspase-1{active}
--
e15
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m15
0
infinite
0
--
csml-variable:Double
m16
0
infinite
0
--
caspase-1{nitrosylated}
--
e17
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m17
0
infinite
0
--
FADD
--
e18
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m18
0
infinite
0
--
csml-variable:Double
m19
0
infinite
0
--
csml-variable:Double
m2
0
infinite
0
--
FasL:Fas
--
e20
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m20
0
infinite
0
--
Fas
--
e21
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m21
0
infinite
0
--
csml-variable:Double
m22
0
infinite
0
--
csml-variable:Double
m23
0
infinite
0
--
csml-variable:Double
m24
0
infinite
0
--
IL-18R
--
e25
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m25
0
infinite
0
--
IL-18:IL-18R
--
e26
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m26
0
infinite
0
--
csml-variable:Double
m27
0
infinite
0
--
csml-variable:Double
m28
0
infinite
0
--
csml-variable:Double
m29
0
infinite
0
--
csml-variable:Double
m3
0
infinite
0
--
IL-18:IL-18R:MyD88
--
e30
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m30
0
infinite
0
--
csml-variable:Double
m31
0
infinite
0
--
MyD88:IRAK
--
e32
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m32
0
infinite
0
--
IL-1R
--
e33
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m33
0
infinite
0
--
csml-variable:Double
m34
0
infinite
0
--
IL-1:IL-1R
--
e35
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m35
0
infinite
0
--
IL-1:IL-1R:MyD88
--
e36
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m36
0
infinite
0
--
csml-variable:Double
m37
0
infinite
0
--
csml-variable:Double
m38
0
infinite
0
--
IRAK:TRAF6
--
e39
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m39
0
infinite
0
--
csml-variable:Double
m4
0
infinite
0
--
--
e40
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m40
0
infinite
0
--
--
e41
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m41
0
infinite
0
--
--
e42
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m42
0
infinite
0
--
--
e43
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m43
0
infinite
0
--
--
e44
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m44
0
infinite
0
--
--
e45
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m45
0
infinite
0
--
--
e46
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytosol
--
--
--
csml-variable:Double
m46
0
infinite
0
--
--
e47
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m47
0
infinite
0
--
IL-12R
--
e48
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m48
0
infinite
0
--
csml-variable:Double
m49
0
infinite
0
--
proIL-18
--
e5
cso30:c:Protein
cso30:i:CC_Cytosol
--
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
--
IL-18
--
e6
cso30:c:Protein
cso30:i:CC_Cytosol
--
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
--
csml-variable:Double
m63
0
infinite
0
--
csml-variable:Double
m64
0
infinite
0
--
csml-variable:Double
m65
0
infinite
0
--
csml-variable:Double
m66
0
infinite
0
--
csml-variable:Double
m67
0
infinite
0
--
TLR4
--
e68
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m68
0
infinite
0
--
LPS:TLR4s
--
e69
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m69
0
infinite
0
--
csml-variable:Double
m7
0
infinite
0
--
csml-variable:Double
m70
0
infinite
0
--
csml-variable:Double
m71
0
infinite
0
--
FADD:FasL:Fas
--
e72
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m72
0
infinite
0
--
csml-variable:Double
m73
0
infinite
0
--
csml-variable:Double
m74
0
infinite
0
--
IL-12:IL-12R
--
e75
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
csml-variable:Double
m75
0
infinite
0
--
TLR2
--
e76
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m76
0
infinite
0
--
LPS:TLR2
--
e77
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
csml-variable:Double
m77
0
infinite
0
--
csml-variable:Double
m78
0
infinite
0
--
csml-variable:Double
m8
0
infinite
0
--
LPS
--
e9
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
csml-variable:Double
m9
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c1 : 1
stoichiometry:c6 : 1
stoichiometry:c2 : 1
m5*m15*0.1
nodelay
--
0
PMID: 10807517 Murine IL-18 is produced as a biologically inactive precursor of 24 kDa (proIL-18), and proIL-18 is cleaved into biologically active mature IL-18 of 18 kDa by caspase-1, originally designated as IL-1-converting enzyme (ICE).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c32 : 1
stoichiometry:c33 : 1
stoichiometry:c37 : 1
m30*m31*0.1
nodelay
--
0
PMID: 10807517 After activation with IL-18, IL-18R recruits MyD88, an adapter protein, providing a platform for the IL-1R associated kinase (IRAK).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c35 : 1
stoichiometry:c36 : 1
m34*m33*0.1
nodelay
--
0
PMID: 10807517, 9354477, 9177292, 9514903 IL-18R shares a signal transducing pathway with IL-1R
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c106 : 1
stoichiometry:c20 : 1
stoichiometry:c107 : 1
m5*m11*0.1
nodelay
--
0
PMID: 10807517, 8999548 Caspase-4 has the capacity to cleave proIL-18 after the 35Asp residue, the same site at which caspase-1 does. However, the efficiency of IL-18 processing by caspase-4 is one hundredth or one thousandth that of caspase-1 (26).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c38 : 1
m31*m36*0.1
nodelay
--
0
PMID: 10807517 After activation with IL-18, IL-18R recruits MyD88, an adapter protein, providing a platform for the IL-1R associated kinase (IRAK).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c44 : 1
m32*0.1
nodelay
--
0
PMID: 10807517 IRAK subsequently undergoes phosphorylation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c46 : 1
stoichiometry:c47 : 1
stoichiometry:c39 : 1
m37*m38*0.1
nodelay
--
0
PMID: 10807517 IRAK subsequently undergoes phosphorylation and interacts with the TNFR-associated factor (TRAF) 6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c50 : 1
stoichiometry:c49 : 1
m8*m39*0.1
nodelay
--
0
PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK) and NFkappaB.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c53 : 1
m7*0.1
nodelay
--
0
PMID: 10807517 IRAK subsequently undergoes phosphorylation and interacts with the TNFR-associated factor (TRAF) 6, leading to nuclear translocation of NFkappaB.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c55 : 1
stoichiometry:c56 : 1
m1*m39*0.1
nodelay
--
0
PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK) and NFkappaB.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c51 : 1
stoichiometry:c67 : 1
m65*m2*0.1
nodelay
--
0
PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK)
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c98 : 1
stoichiometry:c4 : 1
m14*m9*0.1
nodelay
--
0
PMID: 10807517, 9427712 LPS has been reported to have the capacity to induce the activation of caspase-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c66 : 1
m69*0.1
nodelay
--
0
PMID: 10807517, 11513148 mRNA for IL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c90 : 1
stoichiometry:c63 : 1
m49*m75*0.1
nodelay
--
0
PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c60 : 1
m69*0.1
nodelay
--
0
PMID: 10807517 First, mRNA forIL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge. Second,the hepatic IFN-gamma mRNA level is enhanced soon after the elevation of IL-12 p40.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c78 : 1
m69*0.1
nodelay
--
0
PMID: 10807517 IL-18 gene expression may be upregulated by the direct stimulation with microbial products such as LPS
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c68 : 1
stoichiometry:c91 : 1
m9*m76*0.1
nodelay
--
0
PMID: 10807517, 10500213, 10201887, 10549626, 9751057, 9841923, 10426996 LPS is recognized by TLR-4 in mouse and TLR-2 in human.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c69 : 1
stoichiometry:c70 : 1
m9*m68*0.1
nodelay
--
0
PMID: 10807517, 10500213, 10201887, 10549626, 9751057, 9841923, 10426996 LPS is recognized by TLR-4 in mouse and TLR-2 in human.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c73 : 1
m10*0.1
nodelay
--
0
PMID: 10807517 LPS challenge seems to induce rapid secretion of both IL-18 and IL-12 from Kupffer cells, which cause hepatic lymphocytes to produce a huge amount of IFN- gamma, leading to the second elevation of TNF-alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c65 : 1
m63*0.1
nodelay
--
0
PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4, a member of the STAT family,which induces the activation of IFN-gamma gene expression through binding of STAT4 to the corresponding binding site in the IFN-gamma promoter region.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c77 : 1
m26*0.1
nodelay
--
0
PMID: 10807517 After LPS challenge, IL-18 is secreted from Kupffer cells, which initiates the ordered action of IFN-alpha and TNF-alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c80 : 1
m26*0.1
nodelay
--
0
PMID: 10807517 IL-18 accumulated in the liver also induces FasL expression on hepatic effector cells
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1
m16*m15*0.1
nodelay
--
0
PMID: 10807517, 9034139, 9388494 Enzyme activities of some caspases including caspase-1 are reversibly downregulated by nitric oxide (NO), via direct S-nitrosylation of caspase catalytic cysteine residues . Downmodulation of caspase-1 by NO results in reduction of IL-1 and IL-18 secretion from LPS-activated macrophages (59), suggesting a possible negative feedback of IL-18 production by NO.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c79 : 1
stoichiometry:c82 : 1
m20*m18*0.1
nodelay
--
0
PMID: 10807517 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c87 : 1
stoichiometry:c99 : 1
stoichiometry:c85 : 1
m14*m73*m9*0.1
nodelay
--
0
PMID: 10807517, 9491891 Precursor caspase-1 is cleaved into its mature form by caspase-11 or autoproteolytically.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c88 : 1
stoichiometry:c89 : 1
m74*m48*0.1
nodelay
--
0
PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4, a member of the STAT family, which induces the activation of IFN-gamma gene expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c92 : 1
m77*0.1
nodelay
--
0
PMID: 10807517, 11513148 mRNA for IL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c94 : 1
m77*0.1
nodelay
--
0
PMID: 10807517 IL-18 gene expression may be upregulated by the direct stimulation with microbial products such as LPS
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c96 : 1
m77*0.1
nodelay
--
0
PMID: 10807517 First, mRNA forIL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge. Second,the hepatic IFN-gamma mRNA level is enhanced soon after the elevation of IL-12 p40.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c101 : 1
m6*0.1
nodelay
--
0
PMID: 10807517 After LPS challenge, IL-18 is secreted from Kupffer cells, which initiates the ordered action of IFN-alpha and TNF-alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c103 : 1
stoichiometry:c25 : 1
m27*m35*0.1
nodelay
--
0
PMID: 10807517, 10227969, 9759857, 10653850 When IL-18R or IL-1R is activated by corresponding ligand, MyD88 is recruited to the intracellular domain of each receptor.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c109 : 1
stoichiometry:c113 : 1
stoichiometry:c108 : 1
m5*m13*0.1
nodelay
--
0
PMID: 10807517, 8999548, 9334240 Caspase-3 can also cleave IL-18, but at a different site, 69Asp-70Ile, resulting in the accumulation of biologically inactive products (26, 61).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c112 : 1
stoichiometry:c111 : 1
m78*m23*0.1
nodelay
--
0
PMID: 10807517, 8706881, 9463409, 10235259, 9917913 The activated caspase-8 then sequentially activates downstream caspases, such as caspase-3, 6 and 7 (67?70).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c14 : 1
stoichiometry:c13 : 1
m19*m21*0.1
nodelay
--
0
PMID: 10807517 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c16 : 1
stoichiometry:c86 : 1
m24*0.1
nodelay
--
0
PMID: 10807517, 10514014 caspase-1-deficient mice secreted biologically active IL-18 after stimulation with membrane-associated FasL or soluble FasL
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c83 : 1
stoichiometry:c18 : 1
stoichiometry:c5 : 1
m22*m72*0.1
nodelay
--
0
PMID: 10807517, 9521326, 8681377 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c27 : 1
stoichiometry:c72 : 1
stoichiometry:c23 : 1
m25*m70*0.1
nodelay
--
0
PMID: 10807517 IL-18 BP prevents mature IL-18 from binding to its authentic receptor IL-18R,
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c102 : 1
stoichiometry:c26 : 1
m29*m70*0.1
nodelay
--
0
PMID: 10807517 IL-18 BP has the capacity to bind to IL-18 without exhibiting species specificity.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c29 : 1
stoichiometry:c30 : 1
m26*m27*0.1
nodelay
--
0
PMID: 10807517, 10227969, 9759857, 10653850 When IL-18R or IL-1R is activated by corresponding ligand, MyD88 is recruited to the intracellular domain of each receptor.
cso30:c:InputProcess
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