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 an tiinflammatory actions of the glucocorticoids. Subsequent research has shown that the protein plays a major regulatory role in systems as di verse as cell-growth regulation and differentiation, neutrophil migrat ion, CNS responses to cytokines, neuroendocrine secretion and neurodeg eneration. The role of lipocortin-1 in mediating glucocorticoid-induce d effects in these systems has been demonstrated using immunoneutraliz ation strategies and by mimicking steroid actions with highly purified or recombinant lipocortin-l or its biologically active peptide fragme nts. Originally the mode of action of lipocortin-1 seemed to be largel y through inhibition nf prostaglandin formation, but it is now clear t hat it can modify other aspects of cell function, perhaps pointing to a more fundamental mechanism than was originally envisaged. In this ar ticle Rod Flower and Nancy Rothwell review the nature, possible mechan isms and clinical relevance of these diverse actions of lipocortin-1