TY - JOUR
T1 - 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
AU - Nagafuchi, Seiho
AU - Katsuta, Hitoshi
AU - Ohno, Yuju
AU - Inoue, Yasushi
AU - Shimoda, Kazuya
AU - Kogawa, Kazuhiko
AU - Ikeda, Yukari
AU - Koyanagi-Katsuta, Rimiko
AU - Yamasaki, Satoshi
AU - Tominaga, Hiroyuki
AU - Tamiya, Sadafumi
AU - Umemura, Tsukuru
AU - Otsuka, Takeshi
AU - Miyamoto, Toshihiro
AU - Otsuka, Teruhisa
AU - Harada, Mine
AU - Kudoh, Jun
AU - Shimizu, Nobuyoshi
N1 - Funding Information:
We thank Ernest E. Yamashita, for his technical assistance and Dr. Ken Okamura for his help in conducting this research. This work was supported by the Takeda Science Foundation and a Fund for “Research for the Future” Program from the Japan Society for the Promotion of Science (JSPS) and Ministry of Education, Culture, Sports, Science and Technology.
PY - 2005/6/15
Y1 - 2005/6/15
N2 - 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.
AB - 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.
KW - Autoimmune regulator (AIRE)
KW - Epstein-Barr virus (EBV)
KW - Granulo-monocyte colony stimulating factor (GM-CSF)
KW - MAPK inhibitors
KW - Mitogen-activated protein kinase (MAPK)
KW - Ras
KW - Signal transducers and activators of transcription (stat)
KW - p38MAPK
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U2 - 10.1016/j.imlet.2005.02.008
DO - 10.1016/j.imlet.2005.02.008
M3 - Article
C2 - 15894121
AN - SCOPUS:21144439074
SN - 0165-2478
VL - 99
SP - 130
EP - 135
JO - Immunology Letters
JF - Immunology Letters
IS - 1
ER -