Novel aspects of annexin 1 and glucocorticoid biology: intersection with nitric oxide and the lipoxin receptor.
This review will emphasize the concept of anti-inflammation and propose that better understanding of the resolution phase of the inflammatory response organized by the host against inflammatory insults can lead to the identification of novel targets for drug development. Under the umbrella of anti-inflammation, we discuss here recent discoveries in the biology of annexin 1 and glucocorticoids. The fact that annexin 1 and another anti-inflammatory mediator, lipoxin A4, converge onto a specific membrane receptor (termed ALX) might help understanding the resolution phase of inflammation, and strengthen the use of this target for innovative drug development. In addition, glucocorticoids (GC), historically linked to annexin 1, are widely use in the clinical control of several pathologies with an inflammatory etiology, though their use is often burdened by several side effects. The development of new GC with more specific or improved mechanisms, e.g. the nitro-steroids, would go along this wave and, potentially, could be of large applicability. The two mediators/targets here illustrated are to be taken as examples of the clues that the study of anti-inflammation might give to the pharmaceutical industry for innovative drug discovery.
Perretti
Mauro
M
The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. M.Perretti@qmul.ac.uk
D'Acquisto
Fulvio
F
D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D011239:Prednisolone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D044042:Receptors, Formyl Peptide / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000187:drug effects / Q000378:metabolism*
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; C105101:FPR2 protein, human; D005938:Glucocorticoids; D044045:Lipoxins; D020030:Nitric Oxide Donors; D044042:Receptors, Formyl Peptide; D011965:Receptors, Glucocorticoid; D044067:Receptors, Lipoxin; C040527:lipoxin A4; C418962:prednisolone 21-((4'-nitrooxymethyl)benzoate); D009569:Nitric Oxide; D011239:Prednisolone