title: Acteoside inhibits type Ι allergy through the down-regulation of Ca/NFAT and JNK MAPK signaling pathways in basophilic cells.
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.
authors.affiliation: Alliance for Research on North Africa (ARENA), University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Motojima
authors.forename: Myra O
authors.initials: MO
authors.lastname: Villareal
authors.forename: Rieko
authors.initials: R
authors.lastname: Iijima
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology*; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002460:Cell Line; D031671:Cistanche / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D059808:Polyphenols
chemical_list: D018926:Anti-Allergic Agents; D000001:Calcimycin; D061207:Calcium Ionophores; D005960:Glucosides; D015847:Interleukin-4; D048031:JNK Mitogen-Activated Protein Kinases; D050778:NFATC Transcription Factors; D010636:Phenols; D012333:RNA, Messenger; D017455:Receptors, IgE; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha; C058956:acteoside; D059808:Polyphenols; C016658:phorbolol myristate acetate