Original Literature | Model OverView |
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Publication
Title
Macrophage-stimulating protein and RON receptor tyrosine kinase: potentialregulators of macrophage inflammatory activities.
Affiliation
Department of Medicine and Immunology, University of Colorado Health SciencesCenter and Denver Health Medical Center, Denver, CO, USA.ming-hai.wang@uchsc.edu
Abstract
Macrophage-stimulating protein (MSP) is a serum protein belonging to theplasminogen-related growth factor family. The specific receptor for MSP is theRON (recepteur d'origine nantais) receptor tyrosine kinase - a member of the METproto-oncogene family. Activation of RON by MSP exerts dual functions onmacrophages. The stimulatory activities include the induction of macrophagespreading, migration and phagocytosis. However, MSP also inhibitslipopolysaccharide (LPS)-induced production of inflammatory mediators, includinginducible nitric oxide and prostaglandins. These suppressive effects aremediated by RON-transduced signals that block LPS-induced enzymatic cascadesthat activate nuclear factor kappa-B (NFkappaB) pathways. Recent in vivo studiesdemonstrated that inactivation of the RON gene results in increased inflammatoryresponses and susceptibility to LPS-induced septic death in mice, suggestingthat RON expression is required for attenuating the extent of inflammatoryresponses in vivo. Thus, MSP and RON are potential regulators that controlmacrophage activities during bacterial infection in vivo.
PMID
12472665
|
Entity
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PI-3kinase
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Kallikrein
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FctorXIIa
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e14
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csml-variable:Double
m14
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MSP
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e15
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Cell surface proteases
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cso30:c:Protein
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RON receptor{active}:MSP
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inos
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iNOS
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IFN-gamma
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PKR
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e24
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--
csml-variable:Double
m24
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PKR{active}
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STAT1
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e26
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csml-variable:Double
m26
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STAT1{p}
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csml-variable:Double
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csml-variable:Double
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NFKB:IKB
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NFKappB{active}
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csml-variable:Double
m32
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csml-variable:Double
m33
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NFKB{active}
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e34
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protein remnants
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e35
cso30:c:EntityBiological
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NFKB:IKB{p}
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e36
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m36
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csml-variable:Double
m37
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RON receptor:MSP:PI-3kinase
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e38
cso30:c:Complex
cso30:i:CC_Cell
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e4
cso30:c:EntityBiologicalCompartment
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m4
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TNF-alpha
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e40
cso30:c:Protein
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GSNO
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0
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NO
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SP-1
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unknown protein
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cso30:c:Protein
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csml-variable:Double
m45
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0
--
IFN-gamma receptor
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e46
cso30:c:Protein
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IFN-gamma:receptor
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receptor
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cytokine:receptor
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Pro-MSP
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e5
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m5
0
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--
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cso30:c:EntityBiologicalCompartment
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e59
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csml-variable:Double
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RON receptor
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e6
cso30:c:Protein
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csml-variable:Double
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cso30:c:EntityBiologicalCompartment
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TLR4
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cso30:c:Protein
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m64
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LPS:TLR4
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e65
cso30:c:Complex
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TGFbeta
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--
csml-variable:Double
m66
0
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0
--
wortmannin
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e67
cso30:c:SmallMolecule
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csml-variable:Double
m67
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infinite
0
--
TNF-alpha receptor
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e68
cso30:c:Protein
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--
csml-variable:Double
m68
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0
--
TNF_alpha:receptor
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e69
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
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e7
cso30:c:EntityBiologicalCompartment
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--
csml-variable:Double
m7
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receptor
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e70
cso30:c:Protein
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--
csml-variable:Double
m70
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0
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TGFbeta:receptor
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e71
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
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csml-variable:Double
m71
0
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0
--
MyD88
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e72
cso30:c:Protein
cso30:i:CC_Cytosol
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--
csml-variable:Double
m72
0
infinite
0
--
LPS:TLR4:MyD88
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e73
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
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csml-variable:Double
m73
0
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0
--
IRAK
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e74
cso30:c:Protein
cso30:i:CC_Cytosol
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--
csml-variable:Double
m74
0
infinite
0
--
IRAK{active}
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e75
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m75
0
infinite
0
--
csml-variable:Double
m76
0
infinite
0
--
IRF-1
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e77
cso30:c:Protein
cso30:i:CC_Cytosol
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--
csml-variable:Double
m77
0
infinite
0
--
IRF-1{active}
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e78
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m78
0
infinite
0
--
LPS
--
e8
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m8
0
infinite
0
--
cytokine
--
e9
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m9
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c3 : 1
stoichiometry:c32 : 1
stoichiometry:c21 : 1
m19*m11*0.1
nodelay
--
0
PMID: 12472665, 9794431 Wortmannin, a specific inhibitor of PI-3 kinase, prevented the inhibitory effect of RON on iNOS gene transcription activity and NO production induced by LPS and IFN-¦Ã
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c31 : 1
stoichiometry:c30 : 1
stoichiometry:c29 : 1
m20*m49*0.1
nodelay
--
0
The inhibitory effect of MSP on macrophages was first demonstrated in vitro, in which treatment of mouse peritoneal macrophages with physiological concentrations of MSP inhibits lipopolysaccharides (LPS)- or cytokine-induced inducible NO synthase (iNOS) and NO production
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c40 : 1
stoichiometry:c36 : 1
m65*0.1
nodelay
--
0
PMID: 12472665, LPS-induced cyclooxygenase-2 (Cox-2) expression and prostaglandin E2 (PGE2) production by macrophages was also inhibited by MSP
p14
p14
cso30:i:ME_UnknownActivation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c81 : 1
stoichiometry:c42 : 1
m24*m65*0.1
nodelay
--
0
PMID: 12472665, 10557102, 10878375 Recently, it was shown that double-stranded RNA-regulated protein kinase (PKR) also plays a critical role in LPS-induced iNOS expression. Inactivation of PKR gene results in the failure of iNOS induction by LPS
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c82 : 1
stoichiometry:c44 : 1
m25*0.1
nodelay
--
0
PMID: 12472665, 10878375 Inactivation of PKR gene results in the failure of iNOS induction by LPS
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c46 : 1
stoichiometry:c47 : 1
m47*0.1
nodelay
--
0
PMID: 12472665, 10586055 RON activation affect IFN-¦Ã-induced STAT1 phosphorylation and IRF-1 or IRF-2 expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c50 : 1
m47*0.1
nodelay
--
0
PMID: 12472665, 10586055 RON activation affect IFN-¦Ã-induced STAT1 phosphorylation and IRF-1 or IRF-2 expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c51 : 1
m47*0.1
nodelay
--
0
PMID: 12472665, 10586055 RON activation affect IFN-¦Ã-induced STAT1 phosphorylation and IRF-1 or IRF-2 expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c66 : 1
stoichiometry:c53 : 1
stoichiometry:c56 : 1
m34*m47*0.1
nodelay
--
0
PMID: 12472665, 10586055 After LPS and IFN-¦Ã stimulation, nuclear translocation of NF¦ÊB was significantly reduced upon RON activation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c4 : 1
stoichiometry:c10 : 1
m5*m12*0.1
nodelay
--
0
PMID: 12472665, 7508914 Three enzymes, kallikrein, factor XIa and XIIa, in the blood clotting system have the ability to cleave pro-MSP
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c67 : 1
stoichiometry:c77 : 1
stoichiometry:c57 : 1
m34*m65*0.1
nodelay
--
0
PMID: 12472665, 10586055 After LPS and IFN-¦Ã stimulation, nuclear translocation of NF¦ÊB was significantly reduced upon RON activation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c59 : 1
stoichiometry:c63 : 1
stoichiometry:c60 : 1
m31*m32*0.1
nodelay
--
0
PMID: 12472665, 10586055 RON activation also caused decreased binding of NF¦ÊB to its consensus sequence [
p22
p22
cso30:i:ME_UnknownDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c108 : 1
stoichiometry:c54 : 1
stoichiometry:c64 : 1
stoichiometry:c65 : 1
m65*m36*0.1
nodelay
--
0
PMID: 12472665,10837071,10847627, 11521070 In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56] NF¦ÊB is normally sequestered in the cytoplasm by NF¦ÊB inhibitor protein I¦ÊBs such as I¦ÊB¦Á[64]. LPS stimulation causes the degradation of I¦ÊB¦Á, which releases NF¦ÊB, leading to its nuclear translocation [64] Using Raw264.7 cells expressing RON, we demonstrated that MSP treatment significantly prevents the decrease of LPS-induced I¦ÊB¦Á degradationFirst, we found that MSP inhibits LPS-induced I¦ÊB¦Á degradation in macrophages
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c34 : 1
stoichiometry:c74 : 1
m34*0.1
nodelay
--
0
PMID: 12472665, 10837071 LPS stimulation causes the degradation of I¦ÊB¦Á, which releases NF¦ÊB, leading to its nuclear translocation
p25
p25
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c55 : 1
stoichiometry:c129 : 1
stoichiometry:c33 : 1
stoichiometry:c79 : 1
m65*m30*m76*0.1
nodelay
--
0
PMID: 12472665, 9804806 IKK¦Â, also known as IKK1, is the intermediate upstream kinase responsible for the phosphorylation of I¦ÊBs including I¦ÊB¦Á[65]. Reduced phosphorylation and decreased degradation of I¦ÊB¦Á suggest that MSP may affect LPS-induced IKK¦Â activity
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c5 : 1
stoichiometry:c11 : 1
m5*m13*0.1
nodelay
--
0
PMID: 12472665, 7508914 Three enzymes, kallikrein, factor XIa and XIIa, in the blood clotting system have the ability to cleave pro-MSP
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c105 : 1
stoichiometry:c160 : 1
stoichiometry:c93 : 1
m49*0.1
nodelay
--
0
PMID: 12472665, 7514598, 9794431 The inhibitory effect of MSP on macrophages was first demonstrated in vitro, in which treatment of mouse peritoneal macrophages with physiological concentrations of MSP inhibits lipopolysaccharides (LPS)- or cytokine-induced inducible NO synthase (iNOS) and NO production PMID: 12472665, 10725742 Blocking NO production by transforming growth factor-¦Â and MSP prevented LPS-induced inhibition of RON expression
p32
p32
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c39 : 1
stoichiometry:c52 : 1
stoichiometry:c84 : 1
stoichiometry:c86 : 1
stoichiometry:c98 : 1
m45*0.1
nodelay
--
0
Studies of deletion of successive regions, which encompass potential SP-1 sites, suggested that SP-1 or a protein with a binding specificity similar to SP-1 may be involved in the positive regulation of the RON gene transcription PMID: 12472665, 10725742 We have shown that a chemical NO donor, S-nitroglutathione (GSNO) or S-nitroso-N-acetylpenicillamine (SNAP), directly inhibits the RON expression when added to cell culture PMID: 12472665, 10725742 We have shown that in mice injected intraperitoneally with LPS, RON expression is significantly reduced or lost in the peritoneal macrophages [72]. The levels of RON mRNA and protein were also diminished in cultured macrophages following LPS stimulation PMID: 12472665, 10725742 Interestingly, tumour necrosis factor-¦Á together with IFN-¦Ã abrogated the macrophage RON expression, although each individual cytokine alone had no effect
p33
p33
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c35 : 1
stoichiometry:c38 : 1
stoichiometry:c70 : 1
stoichiometry:c80 : 1
stoichiometry:c85 : 1
stoichiometry:c96 : 1
m44*0.1
nodelay
--
0
PMID: 12472665, 9467940, 7632741 Studies of deletion of successive regions, which encompass potential SP-1 sites, suggested that SP-1 or a protein with a binding specificity similar to SP-1 may be involved in the positive regulation of the RON gene transcription PMID: 12472665, 10725742 We have shown that a chemical NO donor, S-nitroglutathione (GSNO) or S-nitroso-N-acetylpenicillamine (SNAP), directly inhibits the RON expression when added to cell culture PMID: 12472665, 10725742 We have shown that in mice injected intraperitoneally with LPS, RON expression is significantly reduced or lost in the peritoneal macrophages [72]. The levels of RON mRNA and protein were also diminished in cultured macrophages following LPS stimulation PMID: 12472665, 10725742 Interestingly, tumour necrosis factor-¦Á together with IFN-¦Ã abrogated the macrophage RON expression, although each individual cytokine alone had no effect
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c100 : 1
stoichiometry:c101 : 1
m46*m23*0.1
nodelay
--
0
PMID: 12472665 IFN-gamma binds its receptor.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c104 : 1
m48*m9*0.1
nodelay
--
0
PMID: 12472665 cytokine binds its receptor
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c106 : 1
stoichiometry:c107 : 1
m8*m64*0.1
nodelay
--
0
PMID: 12472665 LPS binds its receptor.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c121 : 1
stoichiometry:c119 : 1
m65*0.1
nodelay
--
0
PMID: 12472665, 9794431 Wortmannin, a specific inhibitor of PI-3 kinase, prevented the inhibitory effect of RON on iNOS gene transcription activity and NO production induced by LPS and IFN-¦Ã[
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c6 : 1
stoichiometry:c12 : 1
m5*m14*0.1
nodelay
--
0
PMID: 12472665, 7508914 Three enzymes, kallikrein, factor XIa and XIIa, in the blood clotting system have the ability to cleave pro-MSP
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c120 : 1
stoichiometry:c118 : 1
m47*0.1
nodelay
--
0
PMID: 12472665, 9794431 Wortmannin, a specific inhibitor of PI-3 kinase, prevented the inhibitory effect of RON on iNOS gene transcription activity and NO production induced by LPS and IFN-¦Ã[
p41
p41
cso30:i:ME_UnknownProduction
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c131 : 1
stoichiometry:c133 : 1
stoichiometry:c163 : 1
stoichiometry:c27 : 1
stoichiometry:c130 : 1
m65*0.1
nodelay
--
0
PMID: 12472665, 9794431 Wortmannin, a specific inhibitor of PI-3 kinase, prevented the inhibitory effect of RON on iNOS gene transcription activity and NO production induced by LPS and IFN-¦Ã PMID: 12472665, 10725742 Blocking NO production by transforming growth factor-¦Â and MSP prevented LPS-induced inhibition of RON expression PMID: 12472665, 7514598, 9794431 The inhibitory effect of MSP on macrophages was first demonstrated in vitro, in which treatment of mouse peritoneal macrophages with physiological concentrations of MSP inhibits lipopolysaccharides (LPS)- or cytokine-induced inducible NO synthase (iNOS) and NO production
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c128 : 1
stoichiometry:c164 : 1
stoichiometry:c125 : 1
m47*0.1
nodelay
--
0
PMID: 12472665, 9794431 Wortmannin, a specific inhibitor of PI-3 kinase, prevented the inhibitory effect of RON on iNOS gene transcription activity and NO production induced by LPS and IFN-¦Ã PMID: 12472665, 10725742 Blocking NO production by transforming growth factor-¦Â and MSP prevented LPS-induced inhibition of RON expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c136 : 1
m40*m68*0.1
nodelay
--
0
PMID: 12472665 TNF-alpha binds its receptor.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c76 : 1
stoichiometry:c139 : 1
m66*m70*0.1
nodelay
--
0
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c141 : 1
stoichiometry:c140 : 1
stoichiometry:c142 : 1
m72*m65*0.1
nodelay
--
0
PMID: 12472665, 10847627, 11521070 In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56]
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c143 : 1
stoichiometry:c145 : 1
m74*m73*0.1
nodelay
--
0
PMID: 12472665, 10847627, 11521070 In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56]
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c146 : 1
stoichiometry:c75 : 1
stoichiometry:c148 : 1
m75*m37*0.1
nodelay
--
0
PMID: 12472665, 10847627, 11521070 In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56]
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c152 : 1
stoichiometry:c153 : 1
stoichiometry:c156 : 1
m47*m77*0.1
nodelay
--
0
In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56]
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c15 : 1
stoichiometry:c17 : 1
m16*m5*0.1
nodelay
--
0
PMID: 12472665, 8188657, 8609228 Pro-MSP activation was also observed in wound fluids collected from surgical patients [32], presumably mediated by tissue proteases such as epidermal growth factor-binding protein and nerve growth factor-¦Ã[32], or by cell-surface proteases located on tissue macrophages [28].
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c91 : 1
stoichiometry:c155 : 1
m31*0.1
nodelay
--
0
PMID: 12472665, 10847627, 11521070 In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56]
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c157 : 1
stoichiometry:c90 : 1
stoichiometry:c158 : 1
m78*0.1
nodelay
--
0
PMID: 12472665, 10847627, 11521070, 11536325 In mouse macrophages, two separate but cooperative signalling pathways are involved in the induction of iNOS expression: LPS-induced TRL4 > MyD88 > IRAK > IKK > nuclear factor kappa-B (NF¦ÊB) pathway [54, 55] and interferon-¦Ã (IFN-¦Ã)-induced JAK/STAT/IFN-response factor-1 (IRF-1) pathway [54?56]
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c16 : 1
stoichiometry:c159 : 1
m17*m5*0.1
nodelay
--
0
PMID: 12472665, 8188657, 8609228 Pro-MSP activation was also observed in wound fluids collected from surgical patients [32], presumably mediated by tissue proteases such as epidermal growth factor-binding protein and nerve growth factor-¦Ã[32], or by cell-surface proteases located on tissue macrophages [28].
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1
m18*m5*0.1
nodelay
--
0
PMID: 12472665, 8188657, 8609228 Pro-MSP activation was also observed in wound fluids collected from surgical patients [32], presumably mediated by tissue proteases such as epidermal growth factor-binding protein and nerve growth factor-¦Ã[32], or by cell-surface proteases located on tissue macrophages [28].
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c1 : 1
stoichiometry:c23 : 1
m15*m6*0.1
nodelay
--
0
PMID: 12472665, 7939629, 7732008, 8062829 MSP binds the RON receptor.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c89 : 1
stoichiometry:c26 : 1
stoichiometry:c25 : 1
m20*m65*0.1
nodelay
--
0
PMID: 12472665, 7514598, 9794431 The inhibitory effect of MSP on macrophages was first demonstrated in vitro, in which treatment of mouse peritoneal macrophages with physiological concentrations of MSP inhibits lipopolysaccharides (LPS)- or cytokine-induced inducible NO synthase (iNOS) and NO production
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:InputAssociation
threshold
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--
cso30:c:InputProcess
threshold
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--
cso30:c:InputAssociation
threshold
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0
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cso30:c:OutputProcess
threshold
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--
cso30:c:InputAssociation
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:OutputProcess
threshold
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--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
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:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
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,
--
cso30:c:OutputProcess
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
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:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
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:InputProcess
threshold
--
0
1,
--