1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/9917872.csml convertedTime:2009.07.01.11:24

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Tolerance to pyrogens.
Authors Zeisberger E, Roth J.
Affiliation Physiologisches Institut, Klinikum der Justus Liebig Universitat Giessen,Germany. eugen.zeisberger@physiologie.med.uni-giessen.de
Abstract In humans or experimental animals, the repeated confrontation withlipopolysaccharides (LPS) from gram-negative bacteria, but not with muramyldipeptide (MDP) from gram-positive bacteria, leads to attenuation of almost allpathophysiologic effects mediated by proinflammatory cytokines. Our experimentsin guinea pigs and rats demonstrate that attenuation of the febrile responseduring the development of LPS tolerance is associated with a reduced productionof cytokines rather than a decrease in responsiveness to cytokines.Cross-tolerance experiments demonstrate that different stimuli influencingLPS-induced tumor necrosis factor (TNF) release and nitric oxide (NO) synthesiscan modify the development of tolerance. On the other hand, the lack ofcross-tolerance between LPS and MDP indicates that MDP can activate the cytokinecascade and induce the febrile response in animals tolerant to LPS. This mayindicate distinct receptors and signal pathways for LPS and MDP, leading toactivation of the cytokine cascade. LPS tolerance has also been demonstrated inex vivo and in vitro studies. In cultures of monocytes, diminished synthesis ofTNF and NO reported after LPS restimulation could be prevented and reversed byinterferon and granulocyte-macrophage colony-stimulating factor. These findingsadd an additional hypothesis in tolerance development.
PMID 9917872
Model Abstract

Entity

e1: e10: e11:LPS e12:LBP e13:LPS: LBP: CD14-S e14:LPS: LBP: CD14-M e15:LPS: LBP e16:STU e17:LPS: LBP: CD14-M: STU e18:PKC e19:LPS: LBP: CD14-M: STU: PKC e2: e20:p50: p65 e21:p50: p65 {phosphorylated} e22:p50: p65 {nucleus} e23:TNF-alpha e24:TNF-alpha e25:IL-1 e26:IL-6 e27:MDP e28:IL-1 e29:IL-6 e3: e30:IL-1beta e31:IL-1beta e32:p50:p50 {activated} e33:IL-10 e34:IL-4 e35:p50: p50 e4: e5:CD14-M e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:CD14-S e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p3 p4 p5 p6 p7 p8 p9
Model Detail
118.75, 171.9969080091176
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
127.0, 191.0
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
397.5, 23.25
45.0, 25.5

LPS

--

e11

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
157.5, 22.125
45.0, 27.75

LBP

--

e12

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
590.375, 58.5
34.600581012935756, 66.96886647664986

LPS: LBP: CD14-S

--

e13

cso30:c:Complex

cso30:i:CC_Extracellular

--

p2

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
429.375, 155.5
37.876616969962726, 73.30958123218592

LPS: LBP: CD14-M

--

e14

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

p4

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
263.5, 74.125
56.44697122157376, 34.80896558663715

LPS: LBP

--

e15

cso30:c:Protein

cso30:i:CC_Extracellular

--

p1

p2 p3

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
620.375, 169.5
39.46265377855888, 60.711775043936726

STU

--

e16

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p4

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
538.375, 146.5
43.17128919096689, 83.55733391800042

LPS: LBP: CD14-M: STU

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

p5

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
605.5, 307.125
45.0, 33.75

PKC

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
720.375, 146.5
46.64443104582329, 90.27954395965799

LPS: LBP: CD14-M: STU: PKC

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

p16 p18 p19 p20 p21

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
118.75, 171.9969080091176
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
405.625, 364.5
45.24191801366438, 55.3982669555074

p50: p65

--

e20

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p6 p21

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
569.625, 492.5
45.24191801366439, 55.39826695550742

p50: p65 {phosphorylated}

--

e21

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6 p21

p7 p22

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
523.5, 927.0
40.18146975504082, 49.201799700049996

p50: p65 {nucleus}

--

e22

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p7 p22

p8 p10 p11

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
446.0, 1042.0
51.85121107266437, 27.653979238754324

TNF-alpha

--

e23

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p8 p12

p9

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
999.5, 838.0
32.673777420004036, 52.98450392433086

TNF-alpha

--

e24

cso30:c:Protein

cso30:i:CC_Cytosol

--

p9

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
572.0, 1145.0
55.48442906574394, 29.591695501730104

IL-1

--

e25

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p10

p14

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
508.5, 1194.0
54.083044982698965, 28.844290657439448

IL-6

--

e26

cso30:c:mRNA

cso30:i:CC_Nucleolus

--

p11 p13

p15

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
37.5, 507.25
45.0, 25.5

MDP

--

e27

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p6 p12 p13 p22

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
862.125, 1141.5
27.75, 45.0

IL-1

--

e28

cso30:c:Protein

cso30:i:CC_Cytosol

--

p14

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
1002.125, 1209.5
27.75, 45.0

IL-6

--

e29

cso30:c:Protein

cso30:i:CC_Extracellular

--

p15

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
135.87518862352903, 189.12209663264667
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
693.5, 1100.0
45.0, 24.0

IL-1beta

--

e30

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p16

p17

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
1002.125, 1085.5
27.75, 45.0

IL-1beta

--

e31

cso30:c:Protein

cso30:i:CC_Extracellular

--

p17

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
618.5, 634.0
42.500416597233794, 52.041326445592404

p50:p50 {activated}

--

e32

cso30:c:Complex

cso30:i:CC_Cytosol

--

p20

p8 p12

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
601.5, 1020.0
45.0, 24.0

IL-10

--

e33

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p19

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
589.5, 964.0
45.0, 24.0

IL-4

--

e34

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p18

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
838.625, 386.5
41.77982836193968, 51.158973504415926

p50: p50

--

e35

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p20

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
167.5567875770579, 219.09117672382234
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
274.375, 172.5
35.692882249560625, 54.912126537785596

CD14-M

--

e5

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p3

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
300.0, 889.0
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
350.29367619468036, 899.0077409313898
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
306.06992643728904, 894.6363602631969
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
306.93705878547314, 895.503492611381
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
300.0, 889.0
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
300.0, 889.0
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
306.93705878547314, 895.503492611381
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
639.9158804881849, 1062.426469636829
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
563.6082338479803, 1183.8249983826097
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
300.0, 889.0
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
489.375, 12.5
36.3097539543058, 55.86115992970122

CD14-S

--

e6

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p2

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
409.7511016961721, 1076.6637213250547
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
409.25867587120234, 1055.489410851356
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
430.43298634490145, 1114.5805098477247
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
130.0, 177.0
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
133.0, 198.0
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
141.0, 219.0
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
277.0, 21.0
30.0, 30.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e12 e11

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m12*m11*0.1

nodelay

--

true

0

false

PMID: 9917872, 1916089 The LPS binding protein belongs to the acute-phase proteins, and during infection high concentration of the complex between LPS and its binding protein can be formed.

Go back
574.0, 1074.0
44.0, 44.0

p10

p10

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e22

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c27 : 1

m22*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
514.5, 1074.5
42.0, 42.0

p11

p11

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e22

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c28 : 1

m22*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
369.5, 973.5
45.0, 45.0

p12

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e27 e32

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c50 : 1
stoichiometry:c31 : 1

m27*0.1

nodelay

--

true

0

false

PMID: 9917872, 8482846 MDP was a potent inducer of TNF mRNA expression. PMID: 9917872 LPS stimulation in tolerant monocytes and macrophages consists of p50p50 homodimers that blocks transactivation of the TNF gene.

Go back
421.5, 1185.5
45.0, 45.0

p13

p13

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e27

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c33 : 1

m27*0.1

nodelay

--

true

0

false

PMID: 9917872, 9242715 MDP always results in identical circulation levels of TNF and IL-6.

Go back
777.5, 1141.5
45.0, 45.0

p14

p14

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e25

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c37 : 1

m25*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
781.5, 1209.5
45.0, 45.0

p15

p15

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e26

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c38 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes. PMID: 9917872 Daily injection of LPS in rats resulted in a measurable increase in the release of TNF, IL-1beta and IL-6 after the first injection.

Go back
701.0, 1033.0
30.0, 30.0

p16

p16

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e19

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c39 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 9917872 Daily injection of LPS in rats resulted in a measurable increase in the release of TNF, IL-1beta and IL-6 after the first injection.

Go back
785.5, 1085.5
45.0, 45.0

p17

p17

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e30

e31

true true true true

--

and

mass

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

m30*0.1

nodelay

--

true

0

false

PMID: 9917872 Daily injection of LPS in rats resulted in a measurable increase in the release of TNF, IL-1beta and IL-6 after the first injection.

Go back
637.0, 925.0
30.0, 30.0

p18

p18

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e19

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c43 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 9917872 LPS stimulation in tolerant monocytes and macrophages consists of p50p50 homodimers that blocks transactivation of the TNF gene.1.LPS stimulation in tolerant monocytes and macrophages consists of p50p50 homodimers that blocks transactivation of the TNF gene.

Go back
669.0, 981.0
30.0, 30.0

p19

p19

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e19

e33

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c44 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 9917872 LPS stimulation in tolerant monocytes and macrophages consists of p50p50 homodimers that blocks transactivation of the TNF gene.

Go back
405.0, 77.0
30.0, 30.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e15 e6

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m15*m6*0.1

nodelay

--

true

0

false

PMID: 9917872, 7537790 The complex of LPS/LPS-binding protein is bound to a soluble form of the CD14 receptor.

Go back
669.0, 393.0
37.0, 37.0

p20

p20

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e19 e35

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c49 : 1
stoichiometry:c48 : 1

m19*m35*0.1

nodelay

--

true

0

false

Go back
610.0, 414.0
35.0, 35.0

p21

p21

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e19 e20

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c52 : 1
stoichiometry:c53 : 1

m19*m20*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
431.0, 623.0
50.0, 50.0

p7

p22

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e21 e27

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c56 : 1
stoichiometry:c55 : 1

m21*m27*0.1

nodelay

--

true

0

false

PMID: 9917872, 8522354 MDP also results in induction of NFkappaB and its translocation in nucleus.

Go back
353.0, 125.0
30.0, 30.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e5 e15

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m5*m15*0.1

nodelay

--

true

0

false

PMID: 9917872 The next step in LPS-induced cell activation is the interaction between the LPS/LPS-binding protein complex to its CD14 receptor.

Go back
545.0, 101.0
30.0, 30.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e14 e16

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m14*m16*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
617.0, 253.0
30.0, 30.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e17 e18

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
stoichiometry:c15 : 1

m17*m18*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
559.0, 371.0
41.0, 41.0

p6

p6

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e20 e27

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c29 : 1
stoichiometry:c17 : 1

m20*m27*0.1

nodelay

--

true

0

false

PMID: 9917872, 8522354 MDP also results in induction of NFkappaB and its translocation in nucleus.

Go back
518.0, 634.0
50.0, 50.0

p7

p7

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e21

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes.

Go back
449.0, 921.0
46.0, 46.0

p8

p8

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e22 e32

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c51 : 1
stoichiometry:c21 : 1

m22*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes. PMID: 9917872 LPS stimulation in tolerant monocytes and macrophages consists of p50p50 homodimers that blocks transactivation of the TNF gene.

Go back
364.0, 836.0
56.0, 56.0

p9

p9

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e23

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c24 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 9917872, 8330898 The LPS stimulated induction of NFkappaB in the nucleus is essential for expression of cytokine genes, such as TNF, IL-1 and IL-6, with the consequent transcription and translation of these genes. PMID: 9917872 Daily injection of LPS in rats resulted in a measurable increase in the release of TNF, IL-1beta and IL-6 after the first injection.

Go back
203.0, 36.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
467.0, 130.49615951165117

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
579.535242905885, 136.77590564092338

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
559.0, 131.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.0, 212.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
629.0, 290.972366065959

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
647.0, 212.52071204561986

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
451.0, 392.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
582.0, 412.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
640.4631730340566, 237.0

c18

c18

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
554.6349772505464, 548.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
315.0, 36.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
543.0, 684.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
472.0, 967.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
502.95753435061243, 947.8231932086841

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
407.05591181548, 899.3933350374516

c23

c23

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
420.0, 864.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
553.0, 976.0

c25

c25

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
537.4839604832151, 976.0

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
597.0, 1118.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
536.0, 1117.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
83.0, 398.9095480605632

c29

c29

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
292.0, 51.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
415.0, 1013.0

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
69.0, 533.0

c32

c32

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
467.0, 1208.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
67.0, 533.0

c34

c34

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
627.0, 1161.0

c35

c35

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
563.0, 1210.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
823.0, 1164.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
827.0, 1232.0

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
716.0, 1063.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
320.0, 92.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
739.0, 1109.3401177329986

c40

c40

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
716.271200815194, 237.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
831.0, 1108.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
630.897233121606, 953.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
650.8599434057004, 1005.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
654.9809142337788, 237.0

c45

c45

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
685.6004520409521, 237.0

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
694.9870028021417, 237.0

c47

c47

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
646.5393156857681, 430.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
714.0, 412.0

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
441.8823322690734, 51.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
411.3712697136868, 686.0

c50

c50

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
488.03639779959013, 686.0

c51

c51

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
451.0, 397.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
606.029062765764, 449.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
486.81791777096333, 541.0

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
463.0, 673.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
83.0, 527.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
435.0, 92.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
310.0, 156.96188467226233

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
318.0, 109.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
383.0, 150.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back