Glucocorticoid-dependent regulation of galectin-3 expression in alveolar and peritoneal macrophages

SUNDBLAD V; GARCIA L; SALATINO M; ELIA J; LEIMGRUBER C; CROCI D; MALDONADO C; RABINOVICH GA

Congreso; Reunión anual de la SAI; 2010

Galectins is widely expressed tissues where they can regulate different biological processes. Galectin-3 (Gal-3) modulates innate and adaptive immune responses by controlling cell adhesion, chemotaxis, cytokine secretion and apoptosis. Gal-3 may have positive or negative effects on inflammation depending upon tissular and intracellular localization. Glucocorticoids (GCs) are well known regulators of the inflammatory response, acting through multiple and complex mechanisms. In macrophages, GCs inhibit pro-inflammatory genes, leading to a regulatory pattern. However, the effects of GCs on the expression of Gal-3 have not been examined yet. For this purpose, we evaluated the expression of Gal-3 in alveolar (AM) and peritoneal macrophages (PM) in male Wistar rats (n= 9) under different GCs levels. Rats were subjected to adrenalectomy; after 7 days they were injected s.c. for 7 days with 2mg/kg/day dexametasone (ADX-GLU) or its vehicule (ADX). Sham operated rats were CONTROL group. Gal-3 expression in AM was evaluated in lung sections by light and electron immunocytochemistry (IQ), as well as in total homogenate by western blot (WB). PM were purified from CONTROL and ADX by adherent culture on coverslips for Gal-3 immunofluorescence (IF). AM from ADX showed Gal-3 decrease only in cytoplasm at both light and ultrastructural levels (p<0.01vs control), whereas ADX-GLU increased cytoplasmic (p<0,001vs control) and nuclear Gal-3 (p<0,001vs control); changes were verified by WB in total lung. PM isolated from ADX rats also exhibited decreased cytoplasmic Gal-3 by IF. To further address the GCs effects on Gal-3 expression, we stimulated PM from intact rats in vitro with Dexamethasona (10-9 M to 10-7 M), obtaining a dose-dependent increase in PM lysates by WB. Our findings suggest that the constitutive expression of galectin-3 in PM and AM is sustained by GCs, and that Gal-3 may be another mediator by which GCs regulate immunomodulatory response in mucosal defense systems.