title: Mitogen-activated protein kinase pathway controls autoimmune regulator (AIRE) gene expression in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells.
abstract: Autoimmune regulator (AIRE) gene is a responsible gene for the rare autosomal recessive autoimmune disease: autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). Although it has been reported that AIRE is expressed in the thymic epithelial cells and monocyte-dendritic cell lineage, the regulatory mechanisms of AIRE gene expression have as yet been poorly understood. Here we show that the expression of AIRE gene was induced in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells. In GM-CSF-stimulated OTC-4 cells, stat5 was not phosphorylated, while mitogen-activated protein kinases (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated, indicating activation of MAPK pathway. In addition, the expression of AIRE gene was inhibited by specific p38 MAPK inhibitor (SB203580), whereas the expression was rather enhanced by the MEK1/2 inhibitor (U0126), suggesting that AIRE gene expression is regulated by mitogen-activated protein kinase pathway.
authors.affiliation: Laboratory of Molecular Immunology and Diabetes, Department of Health Sciences, School of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. nagafuchi@shs.kyushu-u.ac.jp
authors.forename: Seiho
authors.initials: S
authors.lastname: Nagafuchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katsuta
authors.forename: Yuju
authors.initials: Y
authors.lastname: Ohno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kogawa
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Rimiko
authors.initials: R
authors.lastname: Koyanagi-Katsuta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tominaga
authors.forename: Sadafumi
authors.initials: S
authors.lastname: Tamiya
authors.forename: Tsukuru
authors.initials: T
authors.lastname: Umemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otsuka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Otsuka
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Jun
authors.initials: J
authors.lastname: Kudoh
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D000096927:AIRE Protein