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

Seiho Nagafuchi, Hitoshi Katsuta, Yuju Ohno, Yasushi Inoue, Kazuya Shimoda, Kazuhiko Kogawa, Yukari Ikeda, Rimiko Koyanagi-Katsuta, Satoshi Yamasaki, Hiroyuki Tominaga, Sadafumi Tamiya, Tsukuru Umemura, Takeshi Otsuka, Toshihiro Miyamoto, Teruhisa Otsuka, Mine Harada, Jun Kudoh, Nobuyoshi Shimizu

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11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)130-135
Number of pages6
JournalImmunology Letters
Volume99
Issue number1
DOIs
Publication statusPublished - 2005 Jun 15

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Keywords

  • Autoimmune regulator (AIRE)
  • Epstein-Barr virus (EBV)
  • Granulo-monocyte colony stimulating factor (GM-CSF)
  • MAPK inhibitors
  • Mitogen-activated protein kinase (MAPK)
  • Ras
  • Signal transducers and activators of transcription (stat)
  • p38MAPK

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Nagafuchi, S., Katsuta, H., Ohno, Y., Inoue, Y., Shimoda, K., Kogawa, K., Ikeda, Y., Koyanagi-Katsuta, R., Yamasaki, S., Tominaga, H., Tamiya, S., Umemura, T., Otsuka, T., Miyamoto, T., Otsuka, T., Harada, M., Kudoh, J., & Shimizu, N. (2005). 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. Immunology Letters, 99(1), 130-135. https://doi.org/10.1016/j.imlet.2005.02.008