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Oxygen-regulated transcription factors and their role in pulmonary disease

BioMed Central
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RR0103r03_Semenza.qxd com m entary review reports prim ary research Review Oxygen-regulated transcription factors and their role in pulmonary disease Gregg L Semenza Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Abstract The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, which may have anti-inflammatory activity by counteracting effects of IL-1 and IL-8. EGR-1 controls the production of tissue factor by macrophages, which triggers fibrin deposition in the pulmonary vasculature. HIF-1 activates the expression of the vasoconstrictor endothelin-1 in vascular endothelial cells. Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling. Keywords: EGR-1, HIF-1, NF-IL6, vascular remodeling Received: 27 September 2000 Revisions requested: 10 October 2000 Revisions received: 16 October 2000 Accepted: 19 October 2000 Published: 9 November 2000 Respir Res 2000, 1:159–162 The electronic version of this article can be found online at © Current Science Ltd (Print ISSN 1465-9921; Online ISSN 1465-993X) AP-1 = activator protein-1; ECs = endothelial cells; EGR-1 = early growth response-1; ET-1 = endothelin-1; HIF-1 = hypoxia-inducible factor-1; HMG = high-mobility group; IL = interleukin; NF-IL6 = nuclear factor interleukin-6; PAS = Per/ARNT/Sim; SMC = smooth muscle cell; VEGF = vascular endothelial growth factor. Introduction Chronic lung disease is a major cause of morbidity and mortality in western populations. It is the fourth leading cause of death in the USA, acco

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