Urolithin A represses IgE-induced degranulation in RBL-2H3 cells

Background: Urolithins, intestinal metabolites of ellagic acid, have various physiological properties including anti-inflammatory effects. In addition, the anti-allergic effect of urolithin ingestion in a mouse model of pollinosis has been reported. However, the effect of urolithins on mast cell degranulation has not been reported. To investigate the anti-allergic effect of urolithin A (UA), we examined whether UA suppressed the degranulation reaction in a rat mast cell/basophil cell line, RBL-2H3. Furthermore, we examined the effect of UA on the activation of the signal pathway involved in the degranulation reaction. Methods: We measured antigen-induced β-hexosaminidase and histamine release from RBL-2H3 cells to study the ability of UA to inhibit degranulation activity. Furthermore, we performed western blotting to determine whether Akt phosphorylation, which is involved in the signal transduction pathway leading to antigen-antibody-induced degranulation, was inhibited. Results: UA suppressed β-hexosaminidase activity up to 10 μM in a concentration-dependent manner—2 and 5 μM UA suppressed activity by 46% and 85%, respectively, and 10 μM UA suppressed activity by 96%. The increase in the amount of histamine was also suppressed depending on the concentration of UA—5 and 10 μM of UA suppressed the increase by 60% and 86%, respectively. UA suppressed IgE-mediated Akt phosphorylation in a concentration-dependent manner. Conclusions: UA (10 μM) effectively suppressed the degranulation reaction in RBL-2H3 cells induced by an antigen-antibody reaction. This inhibitory effect was stronger than that of tranilast (50 μM), ketotifen (50 μM), and sodium cromoglicate (50 μM) tested in parallel. Accompanying the antigen-antibody reaction, peak Akt phosphorylation was observed at 20 minutes. UA suppressed Akt phosphorylation in a concentration-dependent manner. This suggests that UA might suppress the degranulation reaction in RBL-2H3 cells by suppressing the signal transduction system associated with the antigen-antibody reaction. Novelty of the Study: This study is the first to report the effect of UA on mast cell degranulation. Additionally, it reveals that UA suppresses IgE-mediated Akt phosphorylation, suggesting a novel mechanism for its anti-allergic properties. These findings provide new insights into UA as a potential therapeutic compound for allergic reactions. Keywords: urolithin A; degranulation; mast cells; anti-allergy; Akt