NR4A orphan nuclear receptor family in peripheral blood eosinophils from patients with atopic dermatitis and apoptotic eosinophils in vitro.
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.
Kagaya
Shinji
S
Genox Research Inc., Bunkyo, Japan.
Hashida
Ryoichi
R
Ohkura
Naganari
N
Tsukada
Toshihiko
T
Sugita
Yuji
Y
Terakawa
Maki
M
Tsujimoto
Gozoh
G
Katsunuma
Toshio
T
Akasawa
Akira
A
Matsumoto
Kenji
K
Saito
Hirohisa
H
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002070:Butadienes / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000097:blood* / Q000235:genetics / Q000276:immunology; D003876:Dermatitis, Atopic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D017730:Ki-1 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood* / Q000235:genetics / Q000276:immunology; D011987:Receptors, Steroid / Q000097:blood* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000097:blood* / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D002070:Butadienes; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D017730:Ki-1 Antigen; C539821:NR4A1 protein, human; D009570:Nitriles; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C113580:U 0126; D019014:fas Receptor; D012313:RNA; D020928:Mitogen-Activated Protein Kinases