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

Area of Science:

• Immunology
• Pharmacology
• Allergy Research

Background:

• Glucocorticoids (GCs) are widely used for their anti-allergic properties, primarily by affecting mast cell signaling.
• The precise mechanisms behind GC-induced mast cell reduction and suppressed activation remain incompletely understood.

Purpose of the Study:

• To investigate the role of the advanced glycation end products (AGEs)/receptors of AGEs (RAGEs) signaling axis in mediating GC-induced mastocytopenia and impaired mast cell degranulation.
• To evaluate the efficacy of AGE and RAGE pathway inhibitors in reversing these effects.

Main Methods:

• Male Wistar rats and Swiss-Webster mice were treated with dexamethasone or prednisolone.
• Animals received aminoguanidine (AGE inhibitor), FPS-ZM1 (RAGE antagonist), or GSC-100 (galectin-3 antagonist).
• Mast cell counts, apoptosis, and histamine release were assessed in vivo and in vitro.

Main Results:

• Aminoguanidine prevented GC-induced mast cell apoptosis and restored mast cell numbers and histamine release.
• FPS-ZM1 and GSC-100 reversed GC-induced mast cell reduction in mice.
• GC treatment increased RAGE and galectin-3 expression, which was inhibited by FPS-ZM1 and GSC-100.

Conclusions:

• GC-induced mastocytopenia and suppressed mast cell activation are linked to the RAGE and galectin-3 signaling pathways.
• Targeting the AGEs/RAGEs axis offers a potential therapeutic strategy for managing GC-related side effects in allergy treatment.