Lipocortin-1: cellular mechanisms and clinical relevance.
Lipocortin-1, a 37 kDa member of the annexin superfamily of proteins, originally evoked interest as one of the 'second messengers' of the anti-inflammatory actions of the glucocorticoids. Subsequent research has shown that the protein plays a major regulatory role in systems as diverse as cell-growth regulation and differentiation, neutrophil migration, CNS responses to cytokines, neuroendocrine secretion and neurodegeneration. The role of lipocortin-1 in mediating glucocorticoid-induced effects in these systems has been demonstrated using immunoneutralization strategies and by mimicking steroid actions with highly purified or recombinant lipocortin-1 or its biologically active peptide fragments. Originally the mode of action of lipocortin-1 seemed to be largely through inhibition of prostaglandin formation, but it is now clear that it can modify other aspects of cell function, perhaps pointing to a more fundamental mechanism than was originally envisaged. In this article Rod Flower and Nancy Rothwell review the nature, possible mechanisms and clinical relevance of these diverse actions of lipocortin-1.
Flower
R J
RJ
Department of Biochemical Pharmacology, Medical College, St Bartholomew's Hospital, London, UK.
Rothwell
N J
NJ
D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D009490:Neurosecretory Systems / Q000378:metabolism; D014018:Tissue Distribution
D017305:Annexin A1