A purified lipocortin shares the anti‐inflammatory effect of glucocorticosteroids in vivo in mice

Abstract

1 The injection of a suspension of a polyacrylamide gel (bio gel) into the dorsal subcutaneous area of mice induced an inflammatory reaction and the migration of neutrophils towards the inflamed site.2 The intravenous administration of anti-inflammatory drugs (dexamethasone, indomethacin and lysine-acetylsalicylate) to polyacrylamide gel-treated mice inhibited the accumulation of neutrophils in the inflamed site. 3 A similar administration of a 36 K mouse lipocortin, induced a strong dose-dependent inhibition of neutrophil accumulation in the inflamed site. 4 Dexamethasone and lipocortin inhibited the production of eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the inflamed site of polyacrylamide gel-treated mice. 5 Lipocortin impaired both phospholipase A2 (PLA2) activity and chemotaxis of isolated inflammatory neutrophils. 6 The present studies show an in vivo anti-inflammatory effect of lipocortin similar to that of glucocorticosteroids. In agreement with recent data on the extracellular effects of various lipocortins, these results might implicate lipocortin(s) in the anti-inflammatory effects of glucocorticosteroids.

Lipocortin 1 mediates dexamethasone-induced growth arrest of the A549 lung adenocarcinoma cell line.

“…During proliferation A549 cells spontaneously release prostaglandin E2 [10][11][12][13][14][15][16][17][18][19][20] ng (28-57 pmol) per ml per 5-day period] into the growth medium. In concentrations that cause growth-arrest, dexamethasone, indomethacin, and lipocortin 1 abolish the generation of this eicosanoid by A549 cells.…”

“…This protein, which is a member of a superfamily of proteins characterized by their ability to bind calcium and anionic phospholipids (14), has a variety of biological actions. For example, systemic administration or extracellular application of the protein inhibits eicosanoid generation (15), cytokineand poly(I)-poly(C)-induced fever (16,17), acute inflammatory oedema (18), neutrophil migration (19), and ischemic damage to the brain (20) and causes differentiation of squamous carcinoma cells (21). In addition, lipocortins may play a role in several other cellular processes including exocytosis (22), chemotaxis (19), anticoagulation (23), growth-factor signal transduction (24,25), cellular differentiation (26), and cell growth (27).…”

Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

“…Lipocortin 1 has anti-inflammatory properites (Cirino et al, 1989;Errasfa & Russo-Marie, 1989) and the observation that its synthesis is regulated by endogenous and exogenous corticosteroids is therefore of great significance. Since lipocortin 2 is also regulated by steroids we propose that this molecule should also be considered as a potential mediator of steroid hormone action.…”

Specific binding of lipocortin‐1 (annexin I) to monocytes and neutrophils is decreased in rheumatoid arthritis

“…In European populations, 40--70% are slow acetylators, whereas in Japanese, only about 10% are slow acetylators (5,6). Although it would be of interest to know the frequency of slow acetylators in Japanese patients with idiopathic SLE, sufficient studies have not been performed.…”