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

• Published in: Immunology letters 2005-06, Vol.99 (1), p.130-135
• Main Authors: Nagafuchi, Seiho, Katsuta, Hitoshi, Ohno, Yuju, Inoue, Yasushi, Shimoda, Kazuya, Kogawa, Kazuhiko, Ikeda, Yukari, Koyanagi-Katsuta, Rimiko, Yamasaki, Satoshi, Tominaga, Hiroyuki, Tamiya, Sadafumi, Umemura, Tsukuru, Otsuka, Takeshi, Miyamoto, Toshihiro, Otsuka, Teruhisa, Harada, Mine, Kudoh, Jun, Shimizu, Nobuyoshi
• Format: Article
• Language: English
• Subjects: AIRE Protein; Autoimmune regulator ( AIRE); Cells, Cultured; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - metabolism; Epstein-Barr Virus Infections - virology; Epstein–Barr virus (EBV); Female; Gene Expression Regulation, Neoplastic - drug effects; Granulo-monocyte colony stimulating factor (GM-CSF); Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Herpesvirus 4, Human - physiology; Humans; Leukemia, Myeloid - genetics; Leukemia, Myeloid - metabolism; MAP Kinase Signaling System - drug effects; MAPK inhibitors; Middle Aged; Mitogen-activated protein kinase (MAPK); Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; p38MAPK; Protein Kinase Inhibitors - pharmacology; Ras; Signal transducers and activators of transcription (stat); Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2005.02.008

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.