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Canna~Fangled Abstracts

Effect of endocannabinoids on IgE-mediated allergic response in RBL-2H3 cells.

By June 5, 2013No Comments
pm1 [Epub ahead of print]

Effect of endocannabinoids on IgE-mediated allergic response in RBL-2H3 cells.


Department of Food and Nutrition, Chungnam National University, Daejeon 305-764, Republic of Korea.


Recently, some endocannabinoids were reported to show anti-inflammatory and anti-allergic activities. In this respect, various arachidonoyl endocannabinoids were screened for the inhibition of allergic response in IgE-activated RBL-2H3 cells. Among arachidonoyl endocannabinoids with a low cytotoxicity, only NA-5HT remarkably inhibited the release of β-hexosaminidase (IC50, 13.58μM), a marker of degranulation, and tumor necrosis factor-α (IC50, 12.52μM), a pro-inflammatory cytokine, in IgE-activated RBL-2H3 cells. Additionally, NA-5HT markedly suppressed the formation of prostaglandin D2 (PGD2) with IC50value of 1.27μM and leukotriene B4 (LTB4) with IC50 value of 1.20μM, and slightly LTC4. When effect of NA-5HT on early stage of FcεRI cascade was investigated, it significantly inhibited phosphorylation of Syk, but not Lyn. Furthermore, NA-5HT suppressed phosphorylation of PLCγ1/2 and PKCδ, related to degranulation process, as well as phosphorylation of LAT, ERK1/2, p38, JNK, Gab2, PI3K and Akt, implicated in the expression of pro-inflammatory cytokines. Relative to its effect on the late stage, NA-5HT slightly reduced phosphorylation of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2). Additionally, NA-5HT significantly reduced the level of p40phox, and partially inhibited the expression of p47phox and p67phox. From these results, it is suggested that NA-5HT expresses anti-allergic action by suppressing the activation of Syk, LAT, p38, JNK, PI3K and Akt, as well as the expression of ERK1/2 and NADPH oxidase subunits. Further, a strong inhibition of PGD2 or LTB4 biosynthesis by NA-5HT may be an additional mechanism for its anti-allergic action. Such anti-allergic actions of NA-5HT may contribute to further information about its biological functions.
Copyright © 2013. Published by Elsevier B.V.




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