Inhibitory Effect of N-Acyl Dopamines on IgE-Mediated Allergic Response in RBL-2H3 Cells
Inhibitory Effect of N-Acyl Dopamines on IgE-Mediated Allergic Response in RBL-2H3 Cells
复制标题
N-酰基多巴胺对 RBL-2H3 细胞中 IgE 介导的过敏反应的抑制作用
作者：
Jae;E. Park;M. Kim;D. Sok
近年来，内源性n -酰基多巴胺被发现具有抗炎和免疫调节作用。然而，n -酰基多巴胺对过敏反应的影响尚未见报道。在这项研究中，我们研究了n -酰基多巴胺是否可能抑制免疫球蛋白e介导的RBL-2H3细胞脱颗粒。当RBL-2H3细胞暴露于微摩尔水平的棕榈酰多巴胺（NP-DA）、油酰多巴胺（NO-DA）或花生四烯醇多巴胺（NA-DA）时，所有这些化合物都能显著抑制β-己糖胺酶（脱颗粒标志物）和肿瘤坏死因子(TNF)-α的释放。NP-DA对β-己糖氨酸酶（IC50, 3.5 μM）和TNF-α (IC50, 2.2 μM)的抑制作用强于NO-DA和NA-DA。此外，NP-DA显著抑制哮喘中促炎脂质介质前列腺素E2、前列腺素D2和白三烯C4的形成。在机制分析中，研究了NP-DA对FcεRI级联的影响，发现NP-DA显著抑制Syk的磷酸化和表达，而Lyn没有。同时，NP-DA也抑制ERK1/2和Akt的磷酸化。此外，NP-DA降低了cPLA2和5-脂氧合酶（5-LO）的磷酸化，但没有降低环氧合酶-2 （COX-2）的磷酸化。以上结果提示，NP-DA可能通过抑制Syk、ERK1/2、Akt、cPLA2和5-LO的激活而发挥抗过敏作用。此外，NP-DA对COX-2活性的强烈抑制可能是其抗过敏作用的另一机制。n -酰基多巴胺的抗过敏作用可能有助于进一步了解n -酰基多巴胺的生物学功能。
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 β-hexosaminidase, a marker of degranulation, as well as tumor necrosis factor (TNF)-α. In comparison, NP-DA, potently suppressing the release of β-hexosaminidase (IC50, 3.5 μM) and TNF-α (IC50, 2.2 μM), was more potent than NO-DA or NA-DA. Additionally, NP-DA markedly suppressed the formation of prostaglandin E2, prostaglandin D2 and leukotriene C4, corresponding to pro-inflammatory lipid mediators in asthma. In the mechanistic analyses, where the effect of NP-DA on the FcεRI 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 cPLA2 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, cPLA2 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.
影响因子：
11.4
作者：
ORTEGA, E;SCHWEITZERSTENNER, R;PECHT, I
通讯作者：
PECHT, I
影响因子：
56.9
作者：
DEVANE, WA;HANUS, L;MECHOULAM, R
通讯作者：
MECHOULAM, R
影响因子：
9.3
作者：
Pandey, Rupal;Mousawy, Khalida;Nagarkatti, Mitzi;Nagarkatti, Prakash
通讯作者：
Nagarkatti, Prakash