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Immunobiology. 2008;213(9-10):899-908. doi: 10.1016/j.imbio.2008.07.016. Epub 2008 Aug 30.

Effects of hypoxia on transcription factor expression in human monocytes and macrophages.

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  • 1Tumour Targeting Group, Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.

Abstract

The presence of multiple areas of hypoxia (low oxygen tension) is a hallmark feature of human and experimental tumours. Monocytes are continually recruited into tumours where they differentiate into tumour-associated macrophages (TAM) and often accumulate in hypoxic and/or necrotic areas. A number of recent studies have shown that macrophages respond to hypoxia by up-regulating transcription factors such as HIF-1alpha and HIF-2alpha, which in turn up-regulate the expression of a broad array of mitogenic, pro-invasive, pro-angiogenic and pro-metastatic genes. Here we show that primary human macrophages but not monocytes rapidly up-regulate HIF-1alpha and HIF-2alpha proteins upon exposure to hypoxia, and that these proteins then translocate to the nucleus. We also demonstrate differences in the temporal expression and responses to re-oxygenation for HIF-1alpha and HIF-2alpha in macrophages. Here we found that, compared to HIF-1alpha, HIF-2alpha expression was prolonged and persisted with re-oxygenation. ATF-4 and Egr-1 were also found to be hypoxia-responsive transcription factors in macrophages but not monocytes, but only early after exposure to hypoxia. Taken together, these findings indicate that a number of transcription factors work together in a tightly regulated fashion to control macrophage activities in ischaemic areas of diseased tissues.

PMID:
18926304
[PubMed - indexed for MEDLINE]
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