The NR4A nuclear receptor family in eosinophils.
It is well-known that many members of the family of nuclear receptors have been implicated in human diseases, and metabolic disorders in particular. The NR4A nuclear receptor family consists of three members, Nur77, Nurr1, and NOR1. All of these are orphan receptors, and Nur77 and NOR1 exert possible pathological roles in immune diseases through the modulation of leukocyte functions. CD30 stimulation, which induces eosinophil-specific apoptosis, markedly enhances expression of Nur77 and NOR1 in eosinophils. This suggests the possibility of pharmacological modulation of Nur77- or NOR1-specific apoptotic pathways via receptor-dependent transactivation. In this review, we discuss treatment of allergic diseases by low molecular weight compounds acting through the NR4A receptor family to cause eosinophil apoptosis. NR4A nuclear receptor genes were selected following comprehensive analysis of differentially expressed genes in eosinophils of atopic dermatitis patients compared with healthy volunteers.
Hashida
Ryoichi
R
Genox Research Inc., Bunkyo, Tokyo, 112-8088, Japan. hashiryo@mail1.accsnet.ne.jp.
Ohkura
Naganari
N
National Cancer Center Research Institute, Chuo, Tokyo, 104-0045, Japan.
Saito
Hirohisa
H
National Research Institute for Child Health and Development, Setagaya, Tokyo, 157-8535, Japan.
Tsujimoto
Gozoh
G
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto, 606-8501, Japan.
D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D018926:Anti-Allergic Agents; D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539882:NR4A2 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015534:Trans-Activators; D014157:Transcription Factors