Inhibitory Effect of Dipeptides Containing Acidic Amino Acid Residue on Degranulation of RBL-2H3 Cells

Upon degranulation, basophils and mast cells secrete an array of inflammatory mediators, including histamine, which leads to not only allergic inflammation but also other inflammatory diseases. We previously reported that an aqueous extract from enzyme-treated, dried sardine inhibits the degranulation of RBL-2H3 cells and attenuates the symptoms of Japanese cedar pollinosis in mice. This study evaluated an antiallergic effect of dipeptides containing acidic amino acid residue in an antigen-induced degranulation assay using RBL-2H3 cells. The result showed that acidic amino acid residue-containing dipeptides inhibit the degranulation of RBL-2H3 cells without cytotoxicity. Additionally, L-histidyl-L-glutamic acid (His-Glu), one of the acidic amino acid residue-containing dipeptides tested in this study, inhibited calcium ionophore-induced degranulation. We also found that His-Glu suppressed microtubule reorganization in RBL-2H3 cells after antigen stimulation. His-Glu slightly, but not significantly, suppressed the elevation of cytosolic calcium ion concentration leading to degranulation. Immunoblot analysis revealed that His-Glu significantly suppressed the phosphorylation of phosphoinositide 3-kinase and Akt, but not that of Syk or phospholipase Cγ. Overall results suggest that acidic amino acid residue-containing dipeptides can be used as food ingredients with an antiallergic effect.