RRC ID 44340
Author Motojima H, Villareal MO, Iijima R, Han J, Isoda H.
Title Acteoside inhibits type Ι allergy through the down-regulation of Ca/NFAT and JNK MAPK signaling pathways in basophilic cells.
Journal J Nat Med
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.
Volume 67(4)
Pages 790-8
Published 2013-10-1
DOI 10.1007/s11418-013-0753-4
PMID 23494816
MeSH Animals Anti-Allergic Agents / chemistry Anti-Allergic Agents / pharmacology* Basophils / drug effects* Basophils / immunology Calcimycin / pharmacology Calcium Ionophores / pharmacology Cell Line Cistanche / chemistry Down-Regulation / drug effects Glucosides / chemistry Glucosides / pharmacology* Humans Hypersensitivity, Immediate / immunology Interleukin-4 / metabolism JNK Mitogen-Activated Protein Kinases / metabolism* MAP Kinase Signaling System / drug effects NFATC Transcription Factors / genetics NFATC Transcription Factors / metabolism Phenols / chemistry Phenols / pharmacology* RNA, Messenger / metabolism Rats Receptors, IgE / genetics Receptors, IgE / metabolism Signal Transduction / drug effects* Tetradecanoylphorbol Acetate / analogs & derivatives Tetradecanoylphorbol Acetate / pharmacology Tumor Necrosis Factor-alpha / metabolism
IF 2.055
Times Cited 16
Human and Animal Cells KU812(RCB0495)