Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics.
The appreciation that the inflammatory reaction does not 'spontaneously' finish, but rather that inflammatory resolution is an active phenomenon brought about by endogenous anti-inflammatory agonists opens multiple opportunities for a reassessment of the complexity of inflammation and its main mediators. This review dwells on one of these pathways, the one centred around the glucocorticoid-regulated protein Annexin A1 and its G protein-coupled receptor. In recent years, much of the knowledge detailing the processes by which Annexin A1 expresses its anti-inflammatory role on innate immunity has been produced. Moreover, the generation of the Annexin A1 null mouse colony has provided important proof-of-concept experiments demonstrating the inhibitory properties of this mediator in the context of inflammatory and/or tissue-injury models. Therefore, Annexin A1 acts as a pivotal homeostatic mediator, where if absent, inflammation would overshoot and be prolonged. This new understanding scientific information could guide us onto the exploitation of the biological properties of Annexin A1 and its receptor to instigate novel drug discovery programmes for anti-inflammatory therapeutics. This line of research relies on the assumption that anti-inflammatory drugs designed upon endogenous anti-inflammatory mediators would be burdened by a lower degree of secondary effects as these agonists would be mimicking specific pathways activated in our body for safe disposal of inflammation. We believe that the next few years will produce examples of such new drugs and the validity of this speculation could then be assessed.
The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, UK. m.perretti@qmul.ac.uk
Mauro
M
Perretti
Jesmond
J
Dalli
D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D051379:Mice
D017305:Annexin A1; D000893:Anti-Inflammatory Agents