Glucocorticoids decrease the numbers and activation of mast cells by inducing the transactivation receptors of AGEs

dc.creatorSantoro, Tassia
dc.creatorAzevedo, Carolina T.
dc.creatorSilva, Patrícia M. R. e
dc.creatorMartins, Marco A.
dc.creatorCarvalho, Vinicius F.
dc.date2019-09-03T16:14:16Z
dc.date2019-09-03T16:14:16Z
dc.date2019
dc.date.accessioned2023-09-26T22:54:12Z
dc.date.available2023-09-26T22:54:12Z
dc.identifierSANTORO, Tassia et al. Glucocorticoids decrease the numbers and activation ofmast cells by inducing the transactivation receptors of AGEs. Journal of Leukocyte Biology, v. 105, p. 131-142, 2019.
dc.identifier0741-5400
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/35317
dc.identifier10.1002/JLB.3A0917-364RR
dc.identifier1938-3673
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8884562
dc.descriptionGlucocorticoids (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.
dc.description2025-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley 12 Months
dc.rightsrestricted access
dc.subjectAlergia
dc.subjectMastócitos
dc.subjectApoptose
dc.subjectMast cells
dc.subjectAllergy
dc.subjectApoptosis
dc.titleGlucocorticoids decrease the numbers and activation of mast cells by inducing the transactivation receptors of AGEs
dc.typeArticle


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