IL-9 and its receptor in allergic and nonallergic lung disease: Increased expression in asthma,☆☆,

https://doi.org/10.1016/S0091-6749(00)90185-4Get rights and content

Abstract

Background: Bronchial asthma is a chronic inflammatory disease associated with genetic components. Recently IL-9 has been reported as a candidate gene for asthma and to be associated with bronchial hyperresponsiveness and elevated levels of total serum IgE. Objective: To investigate the contribution of IL-9 to the pathogenesis of asthma, we examined the expression of IL-9 and its receptor (IL-9R) in bronchial tissue from subjects with atopic asthma (n = 10), chronic bronchitis (n = 11), and sarcoidosis (n = 9) and from atopic (n = 7) and nonatopic (n = 10) healthy control subjects. Methods: Bronchial biopsy specimens were examined for the presence of IL-9 and IL-9R protein and messenger RNA (mRNA) by immunocytochemistry and in situ hybridization, respectively. To phenotype the cells expressing IL-9 in asthmatic tissue, combined in situ hybridization and immunocytochemistry was also performed. Results: There was a highly significant difference (P < .001) in the expression of IL-9 mRNA in asthmatic airways (20.6 ± 4.0 cells/mm of basement membrane) compared with chronic bronchitis (5.6 ± 4.4), sarcoidosis (2.5 ± 1.8), atopic control subjects (7.7 ± 2.2), and healthy control subjects (2.7 ± 2.3). The number of IL-9 immunoreactive cells was also greater in asthmatic patients compared with the other groups (P < .05). Although the level of IL-9R mRNA expression did not differ in any of the groups (P > .05), IL-9R immunoreactivity was significantly higher in asthmatic compared with control subjects. Furthermore, IL-9 mRNA expression levels were also significantly correlated with FEV1 (P < .05) and the airway responsiveness to methacholine producing a 20% fall in FEV1 (P < .01). The cells expressing IL-9 mRNA in asthmatic tissue were CD3+ lymphocytes (68%), major basic protein+ eosinophils (16%), and elastase+ neutrophils (8%). Conclusion: The results of this study demonstrate the potential of IL-9 to be a marker for atopic asthma and furthermore suggest an important role for this cytokine in the pathophysiologic mechanisms of this disease. (J Allergy Clin Immunol 2000;105:108-15.)

Section snippets

Subjects

The subjects in this study were recruited from the outpatient clinic at the Montreal Chest Hospital and from Calmette Hospital, Department of Pneumoimmunoallergy, in Lille, France. Hospital ethics committee approval was obtained for this study, and all participating subjects gave informed written consent before the study. A total of 49 subjects were included in this study. Clinical and demographic characteristics of the patients are shown in Table I.

. Clinical characteristics of study population

Empty CellEmpty Cell

RESULTS

Hybridization between the labeled cRNA probes and mRNA encoding IL-9 and IL-9R were demonstrated by specific deposits of silver grains in the photographic emulsion overlying the tissue sections. As shown in Fig 1, we demonstrated the expression of IL-9 mRNA in all asthmatic (Fig 2, A and B ), atopic, and nonatopic control subjects and subjects with chronic bronchitis (Fig 2, C ) and sarcoidosis.

. IL-9 mRNA expression in nonatopic and atopic control subjects and subjects with atopic asthma,

DISCUSSION

In this study we investigated the in vivo expression of IL-9 in human bronchial tissue obtained from atopic asthmatic patients compared with atopic and nonatopic control subjects and with subjects with chronic bronchitis and sarcoidosis. With use of in situ hybridization and immunocytochemistry staining techniques, our results provide direct evidence that IL-9 is expressed both at the gene and protein level in human airways. Its expression, however, was found to be up-regulated significantly in

Acknowledgements

We thank Elsa Schotman and Dr Rame A. Taha for their technical assistance and instructive discussions.

References (35)

  • T Naseer et al.

    Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy

    Am J Respir Crit Care Med

    (1997)
  • UA Temann et al.

    Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness

    J Exp Med

    (1998)
  • MP McLane et al.

    Interleukin-9 promotes allergen-induced eosinophilic inflammation and airway hyperresponsiveness in transgenic mice

    Am J Respir Cell Mol Biol

    (1998)
  • RC Levitt et al.

    IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders

    J Allergy Clin Immunol

    (1998)
  • IJ Doull et al.

    Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness

    Am J Respir Crit Care Med

    (1996)
  • DS Postma et al.

    Genetic susceptibility to asthma—bronchial hyperresponsiveness coinherited with a major gene for atopy

    N Engl J Med

    (1995)
  • ST Holgate et al.

    Genetic and environmental influences on airway inflammation in asthma

    Int Arch Allergy Immunol

    (1995)
  • Cited by (247)

    • T-cell responses in asthma exacerbations

      2022, Annals of Allergy, Asthma and Immunology
    • Insights into the biology of IL-9 in asthma

      2022, Journal of Allergy and Clinical Immunology
    • Interleukin-9 attenuates inflammatory response and hepatocyte apoptosis in alcoholic liver injury

      2022, Life Sciences
      Citation Excerpt :

      IL-9 is a pleiotropic cytokine that plays a beneficial role in graft tolerance, parasitic infections and tumor immunity. IL-9 can also induce allergic diseases, and the secretion of IL-9 is observed in various immune cells including Th2, Th9, Th17 and Treg cells, NKT cells and mast cells [35]. IL-9 is a secreted protein with a molecular weight of 14 kDa and contains 144 amino acids.

    • Pathology of Asthma

      2021, Encyclopedia of Respiratory Medicine, Second Edition
    View all citing articles on Scopus

    Supported by the Medical Research Council of Canada and by Magainin Pharmaceuticals, Inc.

    ☆☆

    Reprint requests: Qutayba A. Hamid, MD, PhD, Meakins-Christie Laboratories, 3626 St Urbain St, Montreal, Quebec, H2X 2P2 Canada.

    0091-6749/2000 $12.00 + 0  1/1/102692

    View full text