Why is effective treatment of asthma so difficult? An integrated systems biology hypothesis of asthma

Immunology and Cell Biology - Tập 87 Số 8 - Trang 601-605 - 2009
Norbert F. Voelkel1, Sarah Spiegel1
1Department of Biochemistry and Molecular Biology, Pulmonary and Critical Care Medicine Division, Victorial Johnson Center for Obstructive Pulmonary Disease Research, Virginia Commonwealth University Richmond VA USA

Tóm tắt

A hypothesis is presented that asthma is not only an airway disease, but that the disease involves the entire lung, and that the chronicity of asthma and asthma exacerbations can perhaps be explained if one considers asthma as a systemic disease. Increased lung—not only airway—vascularity may be the result of the action of angiogenesis factors, such as vascular endothelial growth factor (VEGF) and sphingosine‐1‐phosphate (S1P). A bone‐marrow lung axis can be postulated as one element of the systemic nature of the asthma syndrome, in which the inflamed lung emits chemotactic signals, which the bone marrow responds to by releasing cells that contribute to lung angiogenesis. A molecular model of the pathobiology of asthma can be built by connecting hypoxia‐inducible transcription factor‐1 alpha, VEGF S1P, and bone‐marrow precursor cell mobilization and acknowledging that angiogenesis is part of the inflammatory response.

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Tài liệu tham khảo

10.1056/NEJMra054308

10.1186/1471-2466-9-7

10.1164/ajrccm.164.10.2103137

10.1007/s11882-009-0001-x

10.1164/rccm.200809-1512OC

10.1016/j.ejphar.2005.12.045

10.1056/NEJMoa012705

10.1042/CS20040342

10.1378/chest.129.4.1068

10.1111/j.1365-2222.2005.02360.x

10.1097/INF.0b013e31818ee0c1

Ou CY, 2008, The role of mycoplasma pneumoniae in acute exacerbation of asthma in children, Acta Paediatr Taiwan, 49, 14

10.1002/ppul.20813

10.1136/thx.2007.090803

10.1056/NEJMoa0808991

10.1038/nri2254

10.1172/JCI36130

10.1016/j.jaci.2007.09.017

10.1111/j.1365-2249.2008.03712.x

10.1136/thx.54.4.283

10.1136/thx.54.4.289

10.1164/ajrccm.156.1.9607066

10.1097/01.all.0000200505.54425.47

10.1046/j.1365-2222.2000.00098.x

Bates DV, 1971, Respiratory Function in Disease

10.1016/S1081-1206(10)60971-4

10.1016/j.jaci.2007.04.021

10.1164/rccm.200801-008OC

10.1152/ajplung.00480.2006

10.1164/ajrccm.164.supplement_2.2106065

10.1016/S0002-9440(10)63369-X

10.1164/rccm.200701-042OC

10.1378/chest.129.2.407

10.1111/j.1365-2222.2006.02547.x

10.1073/pnas.0601057103

10.1165/rcmb.2007-0024OC

10.1196/annals.1413.017

10.1038/nm1770

10.1016/j.jaci.2004.08.009

10.2332/allergolint.R-07-156

10.1016/j.jaci.2008.01.067

10.1007/s10753-004-6047-y

10.1371/journal.pone.0003352

Wakisaka N, 2002, Epstein‐Barr virus latent membrane protein 1 induces and causes release of fibroblast growth factor‐2, Cancer Res, 62, 6337

10.1165/rcmb.2007-0441OC

10.1164/rccm.200506-848OC

10.1038/nature06905

10.1007/s00109-007-0282-2

10.1152/ajplung.00459.2006

10.1189/jlb.0307195

10.1161/01.RES.0000253094.03023.3f

10.1016/j.joca.2004.02.003

10.1101/gad.1471106

10.1074/jbc.M602003200

10.1016/j.ccr.2008.01.034

10.1161/CIRCRESAHA.107.153346

10.1124/mol.108.051516

10.1165/ajrcmb.19.3.3042

Higgins DF, 2007, Hypoxia promotes fibrogenesis in vivo via HIF‐1 stimulation of epithelial‐to‐mesenchymal transition, J Clinic Invest, 117, 3810

10.1152/ajprenal.90209.2008

10.1016/S0946-672X(00)80036-X

10.1016/j.rmed.2008.04.004

10.1164/rccm.200802-315UP

10.1074/jbc.M607065200

10.1152/ajplung.00490.2001

10.1016/j.jaci.2008.07.021

10.1016/j.jaci.2004.11.017

10.1164/rccm.200312-1645OC

10.4049/jimmunol.178.10.6482

10.1111/j.1398-9995.2008.01747.x

10.1111/j.1365-2222.2007.02735.x

10.1182/blood-2006-09-046128

10.1183/09031936.00058907

10.1189/jlb.0906587

10.1186/1465-9921-7-50

10.1182/blood-2006-12-062448

10.1158/0008-5472.CAN-08-1673

10.1164/rccm.200804-595SO

10.1358/dnp.2008.21.2.1188195

10.1038/nri2400

10.1172/JCI12450

10.1161/ATVBAHA.107.143735

10.1358/dnp.2004.17.6.829028

10.1002/jcp.21588

10.1074/jbc.M204764200

10.1124/jpet.106.110718

10.4049/jimmunol.180.6.4323

10.1152/ajplung.00445.2007

10.1089/scd.2004.13.496

10.1124/pr.107.07113

10.1073/pnas.1934494100

10.1182/blood-2004-10-3980

10.1016/j.coph.2005.12.004

10.1164/rccm.200309-1304OC

10.1161/CIRCRESAHA.107.165845

10.1038/nm1238

10.2174/187152807780832256

10.1016/j.bbrc.2008.01.132

10.4049/jimmunol.181.3.1665

10.4049/jimmunol.180.7.4697

10.1096/fj.05-3720fje

10.4049/jimmunol.172.5.2903

10.1016/j.ejphar.2006.11.027

10.1016/j.vph.2005.11.007