NR4A Orphan Nuclear Receptor Family in Peripheral Blood Eosinophils from Patients with Atopic Dermatitis and Apoptotic Eosinophils in vitro

Vol. 137, Suppl. 1, 2005

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Eosinophils in Allergy and Related Diseases.
Editor(s): Makino, S. (Tokyo), Ishikawa, T. (Kumamoto), Fukuda, T. (Tochigi), Ohta, K. (Tokyo), Iwamoto, I. (Chiba), Fujisawa, T. (Mie), Mori, A. (Kanagawa)

Original Paper

NR4A Orphan Nuclear Receptor Family in Peripheral Blood Eosinophils from Patients with Atopic Dermatitis and Apoptotic Eosinophils in vitro
Shinji Kagaya^{a, d}, Ryoichi Hashida^a, Naganari Ohkura^b, Toshihiko Tsukada^b, Yuji Sugita^a, Maki Terakawa^c, Gozoh Tsujimoto^c, Toshio Katsunuma^c, Akira Akasawa^c, Kenji Matsumoto^c, Hirohisa Saito^{c, d}

^aGenox Research Inc., Bunkyo,
^bTumor Endocrinology Project, National Cancer Research Institute, Chuo,
^cDepartment of Allergy and Immunology, National Research Institute for Child Health and Development, Setagaya, Tokyo, and
^dResearch Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan

Address of Corresponding Author

Int Arch Allergy Immunol 2005;137 (Suppl. 1):35-44 (DOI: 10.1159/000085430)

Key Words

Apoptosis
Atopic dermatitis
CD30
Eosinophil
Gene expression
GeneChip
NR4A nuclear receptor family
NOR1
Nur77
Nurr1
Real-time RT-PCR

Abstract

To identify novel genes related to the clinical signs of atopic dermatitis (AD), differentially expressed genes were sought in peripheral blood eosinophils from both AD patients and healthy volunteers. RNA was prepared from eosinophils, expression of various genes was monitored using the Affymetrix GeneChip, and expression was quantified by real-time RT-PCR. Two genes, Nur77 and NOR1, members of NR4A orphan nuclear receptor family, were expressed at a significantly higher level in AD patients than in healthy volunteers. Expression of another gene in the NR4A receptor family, Nurr1, was also higher in AD patients than in healthy volunteers. When peripheral blood leukocytes from healthy volunteers were fractionated, NOR1 expression was highest in eosinophils, but expression of Nur77 and Nurr1 genes was not eosinophil-specific. Extremely intense apoptosis was induced in both eosinophils and an eosinophil cell line, AML14.3D10, by treatment with antibody (Ab) to both CD30 and Fas. Rapid expression of the genes for the NR4A receptor family was observed with anti-CD30 Ab treatment but not with anti-Fas Ab. The NR4A orphan nuclear receptor family gene expression and the subsequent eosinophil apoptosis were downregulated by the MAPK inhibitor, U0126. These results suggest that the expression of the NR4A receptor family genes through CD30 signaling may regulate eosinophil apoptosis in allergic conditions such as AD.

Author Contacts

Correspondence to: Dr. Ryoichi Hashida
Frontier Research Laboratories, Eisai Co., Ltd.
5-1-3 Tokodai
Tsukuba, Ibaraki 300-2635 (Japan)
Tel. +81 29 847 7583, Fax +81 29 847 2037, E-Mail r-hashida@hhc.eisai.co.jp

Article Information

Shinji Kagaya and Ryoichi Hashida contributed equally.

Published online: June 2, 2005
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 2, Number of References : 48

Medline Abstract (ID 15947483)

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