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

VICTORIA SUNDBLAD; LUCIANA GARCÍA; MARIANA SALATINO; JORGE ELÍAS; CAROLINA LEIMGRUBER; DIEGO O. CROCI; CRISTINA MALDONADO; GABRIEL A. RABINOVICH

Buenos Aires

Congreso; 1° Congreso Franco Argentino de Inmunología - LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010

Galectins are expressed in a wide variety of 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 on its tisular 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 yet been examined. Here we evaluated the expression of Gal-3 in alveolar (AM) and peritoneal macrophages (PM) of male Wistar rats (n= 9) exposed to fluctuations in GC levels. Rats were subjected to adrenalectomy; after 7 days they were injected sc for 7 days with 2 mg/kg/day dexametasone (ADX-GLU) or its vehicle control (ADX). Sham operated rats were the CONTROL group. Gal-3 expression in AM was evaluated in lung sections by light and electron immunohistochemistry (IQ), and in total homogenates 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 a decrease in Gal-3 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 effects of GCs on Gal-3 expression, we stimulated PM from intact rats in vitro with Dexamethasona (10-9M to 10-7M). Results revealed a dose-dependent increase in PM lysates by WB. Our findings suggest that 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 the lung mucosal immunity