Targeting hypoxia-A2A adenosine receptor-mediated mechanisms of tissue protection

Despite inflammation having beneficial effects, the action of toxic proinflammatory molecules can result in excessive tissue damage that subsequently contributes to the pathogenesis of many major diseases. The development of novel drugs and therapeutic strategies for the treatment of inflammation requires an improved understanding of the molecular mechanisms that terminate inflammation. The physiological hypothesis proposes that excessive levels of inflammatory tissue damage result in local hypoxia and accumulation of extracellular adenosine. The A(2A) adenosine receptor and hypoxia-inducible factor play important roles in the attenuation of proinflammatory processes in a delayed, negative-feedback manner and thus protect organs from excessive damage. Targeting individual stages of the hypoxia-A(2A) receptor signaling pathway represents an attractive strategy for the modulation of inflammation.