In:
Lipids, Wiley, Vol. 48, No. 4 ( 2013-04), p. 383-393
Abstract:
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 (IC 50 , 3.5 μM) and TNF‐α (IC 50 , 2.2 μM), 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 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 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.
Type of Medium:
Online Resource
ISSN:
0024-4201
,
1558-9307
DOI:
10.1007/s11745-013-3758-6
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2030265-4
detail.hit.zdb_id:
241539-2
SSG:
12
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