/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18031251.csml - 2009.07.01.11:10

Original Literature	Model OverView
Publication Title Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation inrespiratory disease. Authors Sabroe I, Whyte MK. Affiliation Academic Unit of Respiratory Medicine, Section of Infection, Inflammation andImmunity, School of Medicine and Biomedical Sciences, Royal HallamshireHospital, University of Sheffield, Sheffield S10 2JF, U.K.i.sabroe@sheffield.ac.uk Abstract The neutrophil is a crucial early defence against microbial infection, butneutrophilic inflammation can result in devastating acute and chronicinflammatory diseases. In the lungs, the neutrophil is a principal part of thepathology of the acute respiratory distress syndrome, and its activation mayalso be of substantial importance in chronic obstructive pulmonary disease andsome forms of asthma. Induction of neutrophil recruitment in response tomicrobial attack requires activation of TLR (Toll-like receptor)-basedsignalling pathways and the concerted actions of multiple cell types, includingsentinel cells such as monocytes and macrophages acting together with tissuecell types such as the epithelium or smooth-muscle cell. The present reviewdescribes some of these networks and the resulting potential for their targetingin respiratory disease. PMID 18031251

Model Detail

461.0, 1006.0

43.5, 43.5

IL8

G000317

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

p1 p2 p3 p8

csml-variable:Double

m87556

false

infinite

unit

Affymetrix	1369_s_at
Ensembl	ENSG00000169429
HGNC	IL8
OMIM	146930
Proteome	HumanPSD/IL8
RefSeq	NM_000584
TRANSFAC	G000317
Unigene	Hs.551925

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426.0, 915.0

34.0, 34.0

IL-1beta

G010389

cso30:c:mRNA

cso30:i:CC_CellComponent

csml-variable:Double

m93364

false

infinite

unit

TRANSFAC

G010389

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506.0, 786.0

36.0, 36.0

VCAM-1

G010430

cso30:c:mRNA

cso30:i:CC_CellComponent

csml-variable:Double

m93402

false

infinite

unit

TRANSFAC

G010430

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355.0, 724.0

32.0, 32.0

VCAM-1

MO000000308

cso30:c:Protein

cso30:i:CC_CellComponent

csml-variable:Double

m243

false

infinite

unit

InterPro	IPR003987
TRANSPATH	MO000000308

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272.0, 889.0

38.0, 38.0

IL-1beta

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

csml-variable:Double

m1591

false

infinite

unit

TRANSPATH

MO000016597

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110.0, 888.0

39.0, 39.0

LPS

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

p1 p4 p6 p5 p7

csml-variable:Double

m155666

false

infinite

unit

TRANSPATH

MO000016882

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265.0, 1037.0

29.0, 29.0

IL-8

MO000017264

cso30:c:Protein

cso30:i:CC_CellComponent

p1 p2 p3 p8

csml-variable:Double

m2120

false

infinite

unit

InterPro	IPR002473
TRANSPATH	MO000017264

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110.0, 997.0

41.0, 41.0

MO000017793

cso30:c:Protein

cso30:i:CC_CellComponent

csml-variable:Double

m2549

false

infinite

unit

TRANSPATH

MO000017793

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112.0, 1063.0

41.0, 41.0

flagellin

MO000022185

cso30:c:Protein

cso30:i:CC_CellComponent

csml-variable:Double

m6485

false

infinite

unit

TRANSPATH

MO000022185

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188.52277248073258, 46.011693197018275

813.4866586957203, 1201.2739088803078

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

csml-variable:Double

false

infinite

unit

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196.36065979605104, 64.3726086510174

788.5176834328865, 1128.089941752253

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

csml-variable:Double

m10

false

infinite

unit

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109.5, 770.125

37.0, 27.749999999999996

Surfactant protein

e11

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m11

false

infinite

unit

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41.625, 821.5

36.75, 45.0

LPS: Surfactant protein

e12

cso30:c:Complex

cso30:i:CC_Extracellular

csml-variable:Double

m12

false

infinite

unit

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272.125, 1108.5

23.520577581002208, 38.14147715838196

Neutrophil protease

e13

cso30:c:Protein

cso30:i:CC_Extracellular

csml-variable:Double

m13

false

infinite

unit

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188.52277248073258, 46.011693197018275

813.4866586957203, 1201.2739088803078

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

csml-variable:Double

false

infinite

unit

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204.792505654647, 62.55816577112725

780.9471923478917, 1168.1809637320905

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

false

infinite

unit

Go back

234.89151202638874, 91.5144927758177

720.7491796044084, 1110.2683097227086

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

csml-variable:Double

false

infinite

unit

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287.52757093982694, 844.125

37.97242906017308, 23.416331253773393

Tissue factor

cso30:c:Protein

cso30:i:CC_Cytosol

csml-variable:Double

false

infinite

unit

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388.7187816809102, 739.7849091882362

442.38942844499235, 408.0227786834339

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

csml-variable:Double

m50

false

infinite

unit

Go back

436.50013521873046, 749.4544558712146

258.6783622564761, 395.45534196833836

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

csml-variable:Double

m51

false

infinite

unit

Go back

394.48549676306095, 745.2307984314442

430.85599828069115, 397.1310001970178

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

csml-variable:Double

m52

false

infinite

unit

Go back

395.3093132033681, 746.0686275457838

429.2083654000764, 395.45534196833836

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

csml-variable:Double

m53

false

infinite

unit

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388.7187816809102, 739.7849091882362

442.38942844499235, 408.0227786834339

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

csml-variable:Double

m54

false

infinite

unit

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388.7187816809102, 739.7849091882362

442.38942844499235, 408.0227786834339

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

csml-variable:Double

m55

false

infinite

unit

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395.3093132033681, 746.0686275457838

429.2083654000764, 395.45534196833836

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

csml-variable:Double

m56

false

infinite

unit

Go back

711.6548262813515, 907.3507320561762

27.638060778726306, 25.44529011197912

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

csml-variable:Double

m57

false

infinite

unit

Go back

639.1589795343135, 1024.6468080637337

78.26256182918857, 72.05330383321423

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

csml-variable:Double

m58

false

infinite

unit

Go back

388.7187816809102, 739.7849091882362

442.38942844499235, 408.0227786834339

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

csml-variable:Double

m59

false

infinite

unit

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444.5, 844.0

45.0, 24.0

Tissue factor

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

csml-variable:Double

false

infinite

unit

Go back

492.9874808114133, 921.1068605151781

14.009823175868735, 6.860207237450749

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

csml-variable:Double

m60

false

infinite

unit

Go back

492.51965315962343, 900.6480991414583

47.9523343084502, 87.78235984770473

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

csml-variable:Double

m61

false

infinite

unit

Go back

512.6362421865833, 957.7423169285839

7.4852424286361225, 7.612562371616666

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

csml-variable:Double

m62

false

infinite

unit

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199.21080063798502, 50.845714370901305

797.7769714934396, 1149.6573565402728

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

csml-variable:Double

false

infinite

unit

Go back

202.06094147991897, 71.1360557910755

765.3169548808553, 1130.1418162113698

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

csml-variable:Double

false

infinite

unit

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209.66131705840954, 91.42639721124974

761.8228631791528, 1115.3202894796739

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

csml-variable:Double

false

infinite

unit

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333.0, 965.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_Cytosol

G000317 MO000016882

MO000017264

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c7 : 1
stoichiometry:c4 : 1

m87556*m155666*0.1

nodelay

true

false

PMID: 18031251 It has long been known that many cells respond to microbial stimuli such as LPS (lipopolysaccharide), lipoproteins and flagellin by the generation of neutrophil-recruiting chemokines such as IL-8 (interleukin-8).

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332.0, 1006.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

G000317 MO000017793

MO000017264

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c8 : 1
stoichiometry:c5 : 1

m87556*m2549*0.1

nodelay

true

false

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333.0, 1069.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_Cytosol

G000317 MO000022185

MO000017264

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c9 : 1
stoichiometry:c6 : 1

m87556*m6485*0.1

nodelay

true

false

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333.0, 918.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_Cytosol

G010389 MO000016882

MO000016597

and

mass

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

m93364*m155666*0.1

nodelay

true

false

PMID: 18031251, 9670975 Of these, LPS was thought to be a potent stimulator of neutrophil survival, acting again via IL-1beta [39], since it was apparent that LPS-activated neutrophils were themselves a source of IL-1beta, which was an effective stimulator of survival in an autocrine fashion.

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356.0, 789.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_Cytosol

MO000016882 G010430

MO000000308

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
stoichiometry:c18 : 1

m155666*m93402*0.1

nodelay

true

false

PMID: 18031251, 1993838, 7504060 Such co-culture models have been employed previously to demonstrate that monocytes amplify prothrombotic responses to LPS {via production of TF (tissue factor) from endothelial cells [36]}, and can potentially enhance recruitment of other cells through the up-regulation of adhesion molecules such as VCAM (vascular cell adhesion molecule).

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352.0, 841.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_Cytosol

e6 MO000016882

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c15 : 1

m6*m155666*0.1

nodelay

true

false

Go back

116.0, 826.0

30.0, 30.0

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

e11 MO000016882

e12

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c21 : 1

m11*m155666*0.1

nodelay

true

false

PMID: 18031251, 17138954 In part, this is because of a variety of physical defence measures, including the trapping of particulate matter in larger airways by mucus and the ability of various airway-secreted molecules such as surfactant proteins to bind and neutralize LPS.

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334.0, 1114.0

30.0, 30.0

cso30:i:ME_Translation

cso30:i:CC_Cytosol

G000317 e13

MO000017264

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c24 : 1
stoichiometry:c22 : 1

m87556*m13*0.1

nodelay

true

false

PMID: 18031251, 1569186 Neutrophil proteases have the ability to further modify local responses, since they can digest CD14 and decrease LPS responsiveness of some cells, but may also generate IL-8 production from epithelial cells [55] or signal via TLR4.

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