TH2 cytokine–associated transcription factors in atopic and nonatopic asthma: Evidence for differential signal transducer and activator of transcription 6 expression

doi:10.1067/mai.2001.114883

Journal of Allergy and Clinical Immunology

Volume 107, Issue 4, April 2001, Pages 586-591

https://doi.org/10.1067/mai.2001.114883 Get rights and content

Abstract

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. (J Allergy Clin Immunol 2001;107:586-91.)

Section snippets

Patients

Twenty-three subjects were recruited for this study from 3 centers composing the Québec Respiratory Health Network, including the Montreal Chest Institute, Sacré Côeur Hospital, and Laval University, Quebec, Canada. Approval was obtained from the ethical committees of each center, and all subjects gave written informed consent. According to the American Thoracic Society guidelines,³⁰ atopic asthma was defined on the basis of clinical history, positive skin prick test results to 1 or more common

Results

Patient demographics are represented in Table I.

. Patient characteristics

Empty Cell	Control	Nonatopic asthma	Atopic asthma
n	8	7	8
Sex (F/M)	6/2	5/2	4/4
Age (y)*	28.8 ± 7.24	42.9 ± 13.4	29.4 ± 13.2
FEV₁ (L)*	3.34 ± 0.84	2.96 ± 0.83	3.16 ± 1.03
FEV₁ (% predicted)*	97.7 ± 9.35	85.3 ± 19.3	87.9 ± 21.06
PC₂₀ range (μg/mL)	>16	0.11–4.0	0.52–4.0
IgE (IU/mL)*	29.1 ± 12.3	33.8 ± 24.7	643.75 ± 425.1
Inhaled steroid BDP (μg)*	0	1100 ± 547.7	1125 ± 353.6
*Data expressed as mean ± SD.

BDP, Beclomethasone dipropionate.

All patients with asthma had

Discussion

The underlying pathologic differences between atopic and nonatopic asthma remain elusive. Histologically, biopsy material from these 2 groups appears highly similar, and immunocytochemical analyses reveal that the inflammatory cell infiltrate does not seem to differ.² Although there are varying reports on cytokine expression patterns, at least 1 group has observed increased levels of IL-4 in nonatopic asthma and that this expression fails to correlate with pulmonary function.⁵ Furthermore,

Acknowledgements

We thank Patrice Vaillancourt for technical assistance.

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^☆: Supported by Reseau en Santé Respiratoire du FRSQ and Glaxo Wellcome.

^☆☆: Reprint requests: Ron Olivenstein, MD, Montreal Chest Institute, 3650 St Urbain St, Montreal, Quebec, Canada H2X 2P4.

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Rapid PublicationsTH2 cytokine–associated transcription factors in atopic and nonatopic asthma: Evidence for differential signal transducer and activator of transcription 6 expression☆,☆☆

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

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