TH2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression.
BACKGROUND
The expression of IL-4 and IL-5 is increased in patients with atopic asthma compared with control subjects and correlates with indices of pulmonary function. In nonatopic asthma the expression of IL-4, unlike IL-5, fails to correlate with pulmonary function, and compared with their atopic counterparts, these patients have fewer cells expressing IL-4 receptor (IL-4R). As such, a deficiency in the IL-4 signaling pathway may be implicated in nonatopic asthma. The transcription factors GATA-3 and cMAF mediate IL-4 and IL-5 synthesis, whereas signal transducer and activator of transcription 6 (STAT-6) is critical for IL-4R signaling.


OBJECTIVE
This study examines the expression profile of these transcription factors in asthma, according to atopic status.


METHODS
With immunocytochemistry, the expression of GATA-3, cMAF, and STAT-6 protein was determined in sections of bronchial biopsy specimens from patients with atopic asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n = 8).


RESULTS
Higher numbers of cells expressing GATA-3 and cMAF were observed in patients with atopic and those with nonatopic asthma than in control subjects and patients with tuberculosis (P <.001). There were also more STAT-6-immunoreactive cells in patients with atopic and those with nonatopic asthma than in control subjects (P <.0001, P <.05). Notably, however, fewer cells expressing STAT-6 protein were observed in nonatopic versus atopic asthma (P <.0001).


CONCLUSIONS
These results demonstrate the upregulation of GATA-3 and cMAF in both variants of asthma and indicate that reduced IL-4R signaling, because of lower STAT-6 expression, may be a feature of nonatopic asthma.
Christodoulopoulos
P
P
Meakins-Christie Laboratories, McGill University, Sacré-Côeur Hospital, Laval University, Montreal, Quebec, Canada.
Cameron
L
L
Nakamura
Y
Y
Lemière
C
C
Muro
S
S
Dugas
M
M
Boulet
L P
LP
Laviolette
M
M
Olivenstein
R
R
Hamid
Q
Q
D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D050990:GATA3 Transcription Factor; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism*; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051257:Proto-Oncogene Proteins c-maf; D019948:Receptors, Interleukin-4 / Q000502:physiology; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000502:physiology*; D015534:Trans-Activators / Q000032:analysis*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C495607:MAF protein, human; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4