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Acta Physiologica Congress

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Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
3/27/2010-3/30/2010
Copenhagen, Denmark


REGULATION OF HIF-1 ALPHA AND HIF-2 ALPHA IN MONOCYTES BY CHRONIC INFLAMMATION AND HYPOXIA
Abstract number: P-SUN-77

IHNE1 SM, FREDE1 S, FANDREY1 J

Aims: Hypoxia-inducible factors (HIFs) are the key transcription factors for the cellular adaptation to hypoxia. HIFs consist of a constitutive b-subunit and an oxygen- sensitive -subunit (HIF-1a; - 2a; -3a). It was recently shown, that HIF-1a is also regulated by lipopolysaccharides (LPS) and inflammatory cytokines indicating an integrative role for HIFs in conditions of inflammation and hypoxia. Chronic inflammation is characterized by high levels of cytokines independent of an initial stimulus and less oxygen availability. On the other hand inflammatory preconditioning by low concentrations of LPS results in a functional HIF-1a knock out. Therefore we want to examine the temporary course of HIF expression and the HIF-regulating prolyl hydroxylases (PHDs) and possible effects on proliferation, inducibility and morphology in the human monocytic cell line THP-1. Methods: THP-1 cells were kept under normoxic and hypoxic conditions, with or without LPS (1 mg/ml) or IL-1b (300 pg/ml) stimulation for up to 72 hours. Expression of HIF-1a, HIF-2a and PHDs was analysed by RT-PCR, proteins were detected in whole cell lysates by immuno blot. Results: Acute and chronic hypoxia induced HIF- 1a protein accumulation. Moreover LPS increased HIF-1a protein under normoxia which is attended by a reduced cell number and changed cell morphology. Finally, we for the first time show an inflammatory regulation of HIF-2a. Conclusion: Both, HIF-1a and HIF- 2a, are regulated by inflammation. LPS seems to cause a differentiation of monocytic THP-1 cells under normoxia.

To cite this abstract, please use the following information:
Acta Physiologica 2010; Volume 198, Supplement 677 :P-SUN-77

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