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2025-01-01
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- IOC - Artigos de Periódicos [12982]
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GLUCOCORTICOIDS DECREASE THE NUMBERS AND ACTIVATION OF MAST CELLS BY INDUCING THE TRANSACTIVATION RECEPTORS OF AGES
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimmunomodulação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimmunomodulação. Rio de Janeiro, RJ, Brasil.
Abstract
Glucocorticoids (GCs) are potent anti-allergic compounds that function, at least in part, by inhibiting signaling pathways in mast cells. We hypothesized that the GC-induced mastocytopenia and suppression of mast cell activation are mediated by the advanced glycation end products (AGEs)/receptors of AGEs (RAGEs) signaling axis. We evaluated the role of AGEs in GC-mediated mastocytopenia and impaired mast cell degranulation in male Wistar rats and Swiss-Webster mice subcutaneously injected with dexamethasone or prednisolone (0.1 mg/kg) once a day for 21 consecutive days. The animals were treated with either the AGE inhibitor aminoguanidine (250 mg/kg), the RAGE antagonist FPS-ZM1 (1 mg/kg) or the galectin-3 antagonist GSC-100 (1 mg/kg) daily for 18 days, starting 3 days following GC treatment. Aminoguanidine inhibited GC-induced mast cell apoptosis and restored mast cell numbers in the pleural cavity of GC-treated rats. Aminoguanidine also reversed the GC-induced reduction in histamine release triggered by allergens or compound 48/80 in vitro. GC treatment induced RAGE and galectin expression in mast cells, and blocking these agents by FPS-ZM1 or GSC-100 significantly reversed mast cell numbers in the peritoneal cavity and mesenteric tissue of GC-treated mice. In addition, the combination of GC and AGE-induced mast cell apoptosis in vitro was inhibited by both FPS-ZM1 and GSC-100. We concluded that the GC-induced mastocytopenia and suppression of mast cell stimulation are associated with the gene transactivation of RAGE and galectin-3.
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