Inhibitory Effect of N-Acyl Dopamines on IgE-Mediated Allergic Response in RBL-2H3 Cells

Recently, endogenous N-acyl dopamines have been found to show anti-inflammatory and immunomodulatory activities. However, the effect of the N-acyl dopamines on allergic responses was not reported. In this study, we investigated whether N-acyl dopamines might inhibit immunoglobulin E-mediated degranulation in RBL-2H3 cells. When RBL-2H3 cells were exposed to palmitoyl dopamine (NP-DA), oleoyl dopamine (NO-DA) or arachidonoyl dopamine (NA-DA) at micromolar levels, all these compounds significantly inhibited the release of beta-hexosaminidase, a marker of degranulation, as well as tumor necrosis factor (TNF)-alpha. In comparison, NP-DA, potently suppressing the release of beta-hexosaminidase (IC50, 3.5 mu M) and TNF-alpha (IC50, 2.2 mu M), was more potent than NO-DA or NA-DA. Additionally, NP-DA markedly suppressed the formation of prostaglandin E-2, prostaglandin D-2 and leukotriene C-4, corresponding to pro-inflammatory lipid mediators in asthma. In the mechanistic analyses, where the effect of NP-DA on the Fc epsilon RI cascade was examined, NP-DA significantly inhibited the phosphorylation and expression of Syk, but not Lyn. And, NP-DA also suppressed phosphorylation of ERK1/2 and Akt. Further, NP-DA decreased the phosphorylation of cPLA(2) and 5-lipoxygenase (5-LO), but not cyclooxygenase-2 (COX-2). Based on these results, it is suggested that NP-DA exert anti-allergic effect on allergic response through suppressing the activation of Syk, ERK1/2, Akt, cPLA(2) and 5-LO. Besides, a strong inhibition of COX-2 activity by NP-DA may be additional mechanism for its anti-allergic action. Such an anti-allergic action of N-acyl dopamines may contribute to further information about biological functions of N-acyl dopamines.