1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/11841920.csml convertedTime:2009.07.01.10:40

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Iron regulation of hepatic macrophage TNFalpha expression.
Authors Tsukamoto H.
Affiliation USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases and USCResearch Center for Liver Diseases, Keck School of Medicine of University ofSouthern California, Los Angeles, CA 90089, USA. htsukamo@hsc.usc.edu
Abstract Sustained TNFalpha induction is central to the pathogenesis of chronic liverdisease including alcoholic liver disease (ALD). However, molecularunderstanding of this abnormality at the cellular level remains elusive. Redoxregulation of NF-kappaB is critical in the transcriptional control of TNFalphaexpression. Evidence supports that increased iron storage in hepatic macrophages(HM) is causally associated with accentuated and sustained NF-kappaB activationin these cells in ALD. Treatment of cultured HM with a lipophilic iron chelator(deferiprone) abrogates LPS-induced NF-kappaB activation. HM from an animalmodel of ALD have increased nonheme iron content accompanied by increasedgeneration of EPR-detected radicals, NF-kappaB activation, and TNFalphainduction, all of which are normalized by ex vivo treatment of the cells withdeferiprone. A moderate increase in the nonheme iron content in HM byerythrophagocytosis, promotes subsequent LPS-stimulated NF-kappaB activation ina hemeoxygenase-dependent manner. Recent evidence also suggests a role ofintracellular low molecular weight iron in the early signal transduction forLPS-mediated NF-kappaB activation.
PMID 11841920
Model Abstract

Entity

e1: e10: e11:LPS e12:IL-4 e13:IL-10 e14:IL-4 e15:IL-10 e16:Iron e17:e17 e18:e17 e2: e20:NFkappaB e21:NFkappaB{activated} e22:zinc protoporphyrin e23:deferiprone e24:nitrosyl e25:iron:nitrosyl e26:NO e27:TNF-alpha e28:IKK{activated} e29:IKK e3: e30:iNOS{activated} e31:iNOS e32:NADPH oxidase e33:NADPH oxidase{activated} e34:O2- e35:IRP-1 e36:Ferritin e37:4Fe-S4 e38:OH- e39:H2O2 e4: e40:ONOO- e5:TNF-alpha e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:PMA e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p15 p16 p17 p18 p19 p2 p21 p22 p24 p25 p26 p27 p28 p29 p30 p32 p34 p35 p36 p37 p4 p5 p9
Model Detail
89.75, 99.99690800911759
856.2594311764528, 1243.2886940682085

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
98.0, 119.0
829.9775981223105, 1167.545103664102

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
437.5, 779.25
45.0, 25.5

LPS

--

e11

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p1 p2 p12 p15 p16 p24 p25 p32

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
601.5, 880.0
45.0, 24.0

IL-4

--

e12

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p4

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
621.5, 936.0
45.0, 24.0

IL-10

--

e13

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p2

p5

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
821.5, 878.125
45.0, 27.75

IL-4

--

e14

cso30:c:Protein

cso30:i:CC_Cytosol

--

p4

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
825.5, 1014.125
45.0, 27.75

IL-10

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

p5

p1 p9

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
537.875, 577.5
44.25, 45.0

Iron

--

e16

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p15 p30 p10 p21

p4 p5 p9 p11 p16 p29 p22

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
652.0, 364.0
24.0, 24.0

e17

--

e17

cso30:c:ObjectUnknown

cso30:i:CC_Cytosol

--

p28

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
644.0, 516.0
24.0, 24.0

e17

--

e18

cso30:c:ObjectUnknown

cso30:i:CC_Cytosol

--

p30

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
89.75, 99.99690800911759
856.2594311764528, 1243.2886940682085

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
170.125, 665.5
27.75, 45.0

NFkappaB

--

e20

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p11 p12

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
166.125, 577.5
27.75, 45.0

NFkappaB{activated}

--

e21

cso30:c:Protein

cso30:i:CC_Cytosol

--

p11 p12

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
165.5, 747.25
45.0, 25.5

zinc protoporphyrin

--

e22

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p12

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
353.5, 655.25
45.0, 25.5

deferiprone

--

e23

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p11 p12 p15

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
641.5, 594.5
45.0, 27.0

nitrosyl

--

e24

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p16

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
717.875, 641.5
44.25, 45.0

iron:nitrosyl

--

e25

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p16

--

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
493.5, 504.5
52.352941176470594, 31.41176470588236

NO

--

e26

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p26

p11 p12 p19 p28 p35

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
833.5, 635.125
45.0, 33.75

TNF-alpha

--

e27

cso30:c:Protein

cso30:i:CC_Cytosol

--

p32

p18

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
846.125, 453.5
27.75, 45.0

IKK{activated}

--

e28

cso30:c:Protein

cso30:i:CC_Cytosol

--

p17 p18 p19 p29

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
846.125, 533.5
27.75, 45.0

IKK

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p17 p18 p19 p29

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
106.87518862352903, 117.12209663264667
822.0090539293948, 1209.0383168211513

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
333.5, 590.125
45.0, 27.75

iNOS{activated}

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

p24

p12 p15 p26

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
265.5, 450.125
45.0, 27.75

iNOS

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p24

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
429.5, 350.125
45.0, 27.75

NADPH oxidase

--

e32

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p25

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
501.5, 446.125
45.0, 27.75

NADPH oxidase{activated}

--

e33

cso30:c:Protein

cso30:i:CC_Cytosol

--

p25

p27

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
504.875, 280.5
37.80091088829261, 38.44160429317893

O2-

--

e34

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p27

p34 p37 p10

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
757.5, 219.125
45.0, 33.75

IRP-1

--

e35

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p28

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
569.5, 223.125
45.0, 33.75

Ferritin

--

e36

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p10 p21

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
685.875, 461.5
44.25, 45.0

4Fe-S4

--

e37

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p28

p30

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
623.875, 311.5
39.783964129360264, 40.45826860612908

OH-

--

e38

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p36 p22

p21

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
489.5, 169.5
61.029411764705884, 36.61764705882353

H2O2

--

e39

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p34

p22

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
138.55678757705792, 147.09117672382234
758.6458560223374, 1149.1001566387988

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
805.5, 307.5
69.11764705882354, 41.47058823529411

ONOO-

--

e40

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p35 p37

p36

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
409.5, 920.0
45.0, 24.0

TNF-alpha

--

e5

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p1 p9

p32

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
271.0, 817.0
465.6500709748862, 422.29345356567933

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
321.29367619468036, 827.0077409313898
272.27955732982184, 409.2864683429171

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
277.06992643728904, 822.6363602631969
453.51021810030846, 411.0207330392853

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
277.93705878547314, 823.503492611381
451.7759534039399, 409.2864683429171

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
271.0, 817.0
465.6500709748862, 422.29345356567933

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
271.0, 817.0
465.6500709748862, 422.29345356567933

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
277.93705878547314, 823.503492611381
451.7759534039399, 409.2864683429171

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
610.9158804881849, 990.4264696368292
29.091257918298922, 26.33524401024959

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
534.6082338479803, 1111.8249983826097
82.37757307749382, 74.57338194383664

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
271.0, 817.0
465.6500709748862, 422.29345356567933

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
837.5, 391.25
45.0, 25.5

PMA

--

e6

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p17

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
380.7511016961721, 1004.6637213250546
14.746453546866459, 7.100144300343119

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
380.25867587120234, 983.4894108513561
50.4736470593979, 90.85256470691624

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
401.43298634490145, 1042.5805098477247
7.878813199515761, 7.8788131995157675

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
101.0, 105.0
839.7237354966342, 1189.8668429177399

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
104.0, 126.0
805.5569854171277, 1169.6687428256696

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
112.0, 147.0
801.8791759029863, 1154.3288303559784

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
309.0, 917.0
30.0, 30.0

p1

p1

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e11 e15

e5

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c20 : 1
stoichiometry:c3 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 11841920 Addition of LPS to cultured HM results in induced expression of TNF-alpha with its mRNA and protein expression peaking at 2?4 and 6?8 h, respectively. PMID: 11841920, 8386517 IL-10 inhibits TNF-alpha expression at both transcriptional and posttranscriptional levels.

Go back
545.0, 349.0
30.0, 30.0

p10

p10

cso30:i:ME_Reduction

cso30:i:CC_Cytosol

--

e34 e36

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c58 : 1
stoichiometry:c59 : 1

m34*m36*0.1

nodelay

--

true

0

false

PMID: 11841920 iron may be released from ferritin via reduction of iron by O2-.

Go back
273.0, 629.0
30.0, 30.0

p11

p11

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e20 e16 e23 e26

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c31 : 1
stoichiometry:c21 : 1
stoichiometry:c35 : 1
stoichiometry:c27 : 1

m20*m16*0.1

nodelay

--

true

0

false

PMID: 11841920 increased iron content may promote NF-kappaB activation and TNF-alpha expression. PMID: 11841920 When the cells were pretreated with deferiprone, both the transient rise of iron and NF-kappaB activation were abrogated. PMID: 11841920, 9710205, 8626684 In fact, low, physiological concentrations of NO are known to increase TNFalpha- or PMA-induced IKK activity, NF-kappaB binding, and promoter transactivation even though high pharmacological concentrations suppress activation of NF-kappaB.

Go back
273.0, 745.0
30.0, 30.0

p12

p12

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e20 e11 e22 e30 e23 e26

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c30 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1
stoichiometry:c36 : 1
stoichiometry:c37 : 1
stoichiometry:c25 : 1

m20*m11*0.1

nodelay

--

true

0

false

PMID: 11841920, 10600822 LPS treatment results in accentuated NF-kappaB activation, the effect which is abrogated by zinc protoporphyrin, a hemeoxygenase inhibitor. iNOS abolishes LPS-mediated transient rise in LMW iron and NF-kappaB activation. PMID: 11841920 When the cells were pretreated with deferiprone, both the transient rise of iron and NF-kappaB activation were abrogated. PMID: 11841920, 9710205, 8626684 In fact, low, physiological concentrations of NO are known to increase TNFalpha- or PMA-induced IKK activity, NF-kappaB binding, and promoter transactivation even though high pharmacological concentrations suppress activation of NF-kappaB.

Go back
469.0, 685.0
30.0, 30.0

p15

p15

cso30:i:ME_ChangeInMaterialConcentration

cso30:i:CC_Cytosol

--

e11 e30 e23

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c32 : 1
stoichiometry:c5 : 1
stoichiometry:c39 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 11841920 This study demonstrated a transient rise in the intracellular chelatable pool of iron at 10 min following LPS stimulation. iNOS abolishes LPS-mediated transient rise in LMW iron and NF-kappaB activation. PMID: 11841920 When the cells were pretreated with deferiprone, both the transient rise of iron and NF-kappaB activation were abrogated.

Go back
649.0, 649.0
30.0, 30.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e24 e16 e11

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c43 : 1

m24*m16*m11*0.1

nodelay

--

true

0

false

PMID: 118420, 2153975, 2154196 formation of nonheme iron-nitrosyl complex was previously demonstrated in LPS-stimulated macrophages.

Go back
765.0, 429.0
30.0, 30.0

p17

p17

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e29 e6

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c50 : 1
stoichiometry:c45 : 1

m29*m6*0.1

nodelay

--

true

0

false

PMID: 11841920, 9710205 In fact, low, physiological concentrations of NO are known to increase TNF-alpha- or PMA-induced IKK activity, NF-kappaB binding.

Go back
769.0, 589.0
30.0, 30.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e29 e27

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c51 : 1
stoichiometry:c47 : 1

m29*m27*0.1

nodelay

--

true

0

false

PMID: 11841920, 9710205 In fact, low, physiological concentrations of NO are known to increase TNF-alpha- or PMA-induced IKK activity, NF-kappaB binding.

Go back
765.0, 541.0
30.0, 30.0

p19

p19

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e29 e26

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c18 : 1
stoichiometry:c49 : 1

m29*m26*0.1

nodelay

--

true

0

false

PMID: 11841920, 9710205 In fact, low, physiological concentrations of NO are known to increase TNF-alpha- or PMA-induced IKK activity, NF-kappaB binding.

Go back
525.0, 933.0
30.0, 30.0

p2

p2

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e11

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c4 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 11841920 Addition of LPS to cultured HM results in induced expression of TNF-alpha with its mRNA and protein expression peaking at 2?4 and 6?8 h, respectively. Induction of IL-10 lags slightly behind that of TNF-alpha.

Go back
601.0, 389.0
30.0, 30.0

p21

p21

cso30:i:ME_Oxidation

cso30:i:CC_Cytosol

--

e36 e38

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c82 : 1
stoichiometry:c77 : 1

m36*m38*0.1

nodelay

--

true

0

false

PMID: 11841920 iron may be released from ferritin via reduction of iron by O2- or oxidative destruction of ferritin proteins by OH.

Go back
629.0, 173.0
30.0, 30.0

p22

p22

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e39 e16

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c85 : 1
stoichiometry:c84 : 1

m39*m16*0.1

nodelay

--

true

0

false

PMID: 11841920, 9512778, 10391125, 10678585 iron may produce OH from H2O2 generated from O2-.

Go back
341.0, 449.0
30.0, 30.0

p24

p24

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e31 e11

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c66 : 1
stoichiometry:c65 : 1

m31*m11*0.1

nodelay

--

true

0

false

PMID: 11841920 LPS stimulates activities of iNOS and NADPH oxidase.

Go back
437.0, 445.0
30.0, 30.0

p25

p25

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e32 e11

e33

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c69 : 1
stoichiometry:c68 : 1

m32*m11*0.1

nodelay

--

true

0

false

PMID: 11841920 LPS stimulates activities of iNOS and NADPH oxidase.

Go back
469.0, 557.0
30.0, 30.0

p26

p26

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e30

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c87 : 1

m30*0.1

nodelay

--

true

0

false

PMID: 11841920 LPS stimulates activities of iNOS and NADPH oxidase resulting in generation of NO and O2-.

Go back
509.0, 381.0
30.0, 30.0

p27

p27

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e33

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c73 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 11841920 LPS stimulates activities of iNOS and NADPH oxidase resulting in generation of NO and O2-.

Go back
693.0, 361.0
30.0, 30.0

p28

p28

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e35 e26

e37 e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c13 : 1
stoichiometry:c75 : 1
stoichiometry:c33 : 1

m35*m26*0.1

nodelay

--

true

0

false

PMID: 11841920, 7557022 NO may target and release iron sulfur clusters from enzymes containing them. One such enzyme is iron regulatory protein-1 (IRP-1).

Go back
765.0, 485.0
30.0, 30.0

p29

p29

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e29 e16

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c17 : 1
stoichiometry:c79 : 1

m29*m16*0.1

nodelay

--

true

0

false

PMID: 11841920 A transiently raised LMW-iron may directly provide redox modifications of signaling proteins for IKK activation.

Go back
625.0, 473.0
30.0, 30.0

p30

p30

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e37

e16 e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c81 : 1
stoichiometry:c34 : 1

m37*0.1

nodelay

--

true

0

false

PMID: 11841920, 7557022 NO may target and release iron sulfur clusters from enzymes containing them. One such enzyme is iron regulatory protein-1 (IRP-1).

Go back
601.0, 761.0
30.0, 30.0

p32

p32

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

e5 e11

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c90 : 1
stoichiometry:c89 : 1

m5*m11*0.1

nodelay

--

true

0

false

PMID: 11841920 Addition of LPS to cultured HM results in induced expression of TNF-alpha with its mRNA and protein expression peaking at 2?4 and 6?8 h, respectively.

Go back
505.0, 225.0
30.0, 30.0

p34

p34

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e34

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c92 : 1

m34*0.1

nodelay

--

true

0

false

PMID: 11841920, 9512778, 10391125, 10678585 iron may produce OH from H2O2 generated from O2-.

Go back
761.0, 377.0
30.0, 30.0

p35

p35

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e26

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c95 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 11841920 OH is also produced from ONOO- generated from NO and O2.

Go back
689.0, 313.0
30.0, 30.0

p36

p36

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e40

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c96 : 1

m40*0.1

nodelay

--

true

0

false

PMID: 11841920 OH is also produced from ONOO- generated from NO and O2.

Go back
761.0, 285.0
30.0, 30.0

p37

p37

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e34

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c99 : 1

m34*0.1

nodelay

--

true

0

false

PMID: 11841920 OH is also produced from ONOO- generated from NO and O2.

Go back
753.0, 877.0
30.0, 30.0

p4

p4

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e12 e16

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c11 : 1
stoichiometry:c8 : 1

m12*m16*0.1

nodelay

--

true

0

false

PMID: 11841920, 9180188 Iron overloading in mice causes suppressed candidacidal activity by macrophages and reduced release of NO and IL-12 and enhanced production of IL-4 and IL-10 by splenic CD4+ T cells.

Go back
757.0, 933.0
30.0, 30.0

p5

p5

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e13 e16

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c12 : 1
stoichiometry:c10 : 1

m13*m16*0.1

nodelay

--

true

0

false

PMID: 11841920, 9180188 Iron overloading in mice causes suppressed candidacidal activity by macrophages and reduced release of NO and IL-12 and enhanced production of IL-4 and IL-10 by splenic CD4+ T cells.

Go back
417.0, 865.0
30.0, 30.0

p9

p9

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e16 e15

e5

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c19 : 1
stoichiometry:c22 : 1

m16*0.1

nodelay

--

true

0

false

PMID: 11841920 increased iron content may promote NF-kappaB activation and TNF-alpha expression.

Go back
344.57955032067656, 805.0

c1

c1

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
786.0, 963.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
576.0, 623.0

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
574.0, 623.0

c12

c12

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
540.0, 392.8596008605664

c13

c13

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
546.0, 403.56437778390165

c14

c14

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
582.0, 510.304423313236

c17

c17

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
546.0, 524.0

c18

c18

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
450.76809101250774, 886.3421960070938

c19

c19

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
467.0, 805.0

c2

c2

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
342.9348316557542, 935.7190965448914

c20

c20

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
306.8573045916685, 649.0588679271247

c21

c21

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
432.0, 895.0

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
442.33530683861255, 623.0

c23

c23

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
198.0, 698.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
198.48678516135612, 627.6233495239067

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
198.0, 653.1395094803822

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
201.41479705834084, 609.003462099581

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
211.0, 760.0

c28

c28

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
296.58961861282455, 618.0

c29

c29

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
339.0, 932.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
310.8662560398757, 764.4567140814585

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
310.8974170817106, 604.0

c31

c31

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
374.0, 618.0

c32

c32

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
684.0, 376.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
646.0, 503.0

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
306.52838850391703, 534.0

c35

c35

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

1

1,

--

Go back
304.7831808633081, 681.0

c36

c36

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
305.7798512445709, 536.0

c37

c37

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

1

1,

--

Go back
463.0, 722.731881015412

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
496.0, 629.3752370762162

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
555.0, 948.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
664.0, 622.0

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
582.0, 614.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
480.0, 677.2508001254068

c42

c42

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
679.0, 664.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
795.6499055497528, 465.5098677696539

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.0, 450.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
805.7433776766208, 565.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
793.0, 505.85994340570034

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
803.0, 556.0

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.0, 495.65685424949237

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
399.0, 675.0

c5

c5

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
802.1219853038187, 415.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
805.6856438376102, 618.3934230932867

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
535.0, 319.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
566.019375177176, 257.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
560.0, 379.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
594.0, 257.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
311.0, 464.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
356.0, 479.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
363.41513363755524, 486.62673780280596

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
452.0, 378.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
467.0, 460.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
452.21045345670586, 482.99723135482276

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
647.0, 892.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
524.0, 419.0

c72

c72

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
524.0, 327.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
719.6304174085473, 253.0

c74

c74

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
708.0, 391.0

c75

c75

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
568.2232910197988, 419.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
801.5357429061181, 514.6134655807892

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.0, 482.2573305919324

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
783.0, 892.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
662.9834024717477, 485.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
580.616885012987, 503.0

c81

c81

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
624.8311367793272, 352.0

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
551.0, 188.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
644.0, 203.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
565.0, 210.84059882438402

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
379.0, 577.8996247238159

c86

c86

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
494.0, 542.5098677696539

c87

c87

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
446.0, 794.1640028712568

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
631.0, 667.6476846184182

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
667.0, 948.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
483.0, 778.8093848167788

c90

c90

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
521.613571991078, 262.97643588401263

c91

c91

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
520.0, 214.0

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
791.0, 354.65685424949237

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
671.974522228289, 329.0

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
727.0, 328.0

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
543.0, 300.0

c98

c98

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
791.0, 307.0

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back