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Acteoside inhibits type Ι allergy through the down-regulation of Ca/NFAT and JNK MAPK signaling pathways in basophilic cells

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Abstract

We have previously reported that acteoside inhibits the release of β-hexosaminidase from immunoglobulin E (IgE)-sensitized and bovine serum albumin-stimulated rat basophilic leukemia cells as well as the intracellular calcium level, release of histamine from, and production of tumor necrosis factor-alpha and interleukin-4 in human basophilic (KU812) cells. However, the molecular mechanism underlying the anti-allergic effects of acteoside has not yet been elucidated. Here, we used microarray analysis to determine the global gene expression profile of KU812 cells treated with acteoside and calcium ionophore A23187 plus phorbol-12-myristate 13-acetate (A23187+PMA), and the results were validated by real-time polymerase chain reaction (PCR) and Western blotting. Microarray analysis results showed that of the 201 genes in the microarray, 149 genes were up-regulated, while 52 genes were down-regulated. The significantly down-regulated genes have functions as chemokine and IgE receptors, as well as for immune response. Results of the validation of the microarray results using real-time PCR showed a significant decrease in the expressions of Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide (FCER1A) and nuclear factor of activated T cell, cytoplasmic, calcineurin-dependent 1 (NFATC1) genes. Furthermore, Western blotting showed a decrease in the phosphorylation of mitogen-activated protein kinase (MAPK) Jun N terminal kinase (JNK), revealing the role of JNK MAPK in acteoside-mediated allergy inhibition. We determined that the anti-allergy effects of acteoside were due to the down-regulation of the expressions of the chemokine ligand 1 (CCL1), CCL2, CCL3, CCL4, FCER1A and NFATC1 genes and the inhibition of the MAPK pathway through decreased JNK phosphorylation.

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Abbreviations

IgE:

Immunoglobulin E

BSA:

Bovine serum albumin

RBL-2H3:

Rat basophilic leukemia

[Ca2+]i :

Intracellular calcium

TNF-α:

Tumor necrosis factor-alpha

FcεRI:

High-affinity IgE receptors

IL:

Interleukin

KU812:

Human basophilic

A23187+PMA:

Calcium ionophore A23187 plus phorbol-12-myristate 13-acetate

PCR:

Polymerase chain reaction

FCER1A :

Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide

NFATC1 :

Nuclear factor of activated T cell, cytoplasmic, calcineurin-dependent 1

MAPK:

Mitogen-activated protein kinase

JNK:

c-Jun N terminal kinase

CCL :

Chemokine ligand

ERK:

Extracellular signal-regulated kinase

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Acknowledgments

This work was supported in part by the Japan Science and Technology (JST). We also would like to thank Dr. Parida Yamada for her contribution to the animal cell experiment.

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Authors and Affiliations

  1. Alliance for Research on North Africa (ARENA), University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8572, Japan

    Hideko Motojima, Myra O. Villareal, Junkyu Han & Hiroko Isoda

  2. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8572, Japan

    Rieko Iijima

  3. Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8572, Japan

    Junkyu Han & Hiroko Isoda

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  1. Hideko Motojima
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Correspondence to Hiroko Isoda.

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Motojima, H., Villareal, M.O., Iijima, R. et al. Acteoside inhibits type Ι allergy through the down-regulation of Ca/NFAT and JNK MAPK signaling pathways in basophilic cells. J Nat Med 67, 790–798 (2013). https://doi.org/10.1007/s11418-013-0753-4

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