Hypoxia and inflammation

Abstract

Uncontrolled or non-resolving inflammation is central to the pathophysiology of clinically important conditions including inflammatory bowel disease (IBD), psoriasis, atherosclerosis and arthritis. A combination of increased oxygen demand and decreased supply renders the local microenvironment of chronically inflamed tissues oxygen deprived (hypoxic), leading to the expression of a programme of genes that promote adaptation to the hypoxic challenge. This ancient and ubiquitous adaptive transcriptional pathway is governed by a transcription factor termed the hypoxia-inducible factor (HIF). Originally identified in the search for regulators of hypoxia-induced erythropoietin expression and adaptation to high altitude, HIF has been more recently recognized as a major regulator of immune cell function, which is central to the control of immunity and inflammation. Indeed, recent studies have demonstrated that the use of drugs targeting the HIF pathway may be of benefit in the treatment of chronic inflammatory disease.