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.
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.
Nagafuchi
Seiho
S
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
Katsuta
Hitoshi
H
Ohno
Yuju
Y
Inoue
Yasushi
Y
Shimoda
Kazuya
K
Kogawa
Kazuhiko
K
Ikeda
Yukari
Y
Koyanagi-Katsuta
Rimiko
R
Yamasaki
Satoshi
S
Tominaga
Hiroyuki
H
Tamiya
Sadafumi
S
Umemura
Tsukuru
T
Otsuka
Takeshi
T
Miyamoto
Toshihiro
T
Otsuka
Teruhisa
T
Harada
Mine
M
Kudoh
Jun
J
Shimizu
Nobuyoshi
N
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
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D000096927:AIRE Protein