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Increased Expression of IL-33 in Severe Asthma: Evidence of Expression by Airway Smooth Muscle Cells¹

David Préfontaine,^* Stéphane Lajoie-Kadoch,^* Susan Foley,^* Séverine Audusseau,^* Ron Olivenstein, Andrew J. Halayko, Catherine Lemière, James G. Martin,^* and Qutayba Hamid^2*

^*Meakins-Christie Laboratories, Faculty of Medicine and Montreal Chest Hospital Research Institute, McGill University, Montreal, Quebec, Canada; Department of Physiology and Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; and Sacré-Coeur Hospital, University of Montreal, Montreal, Quebec, Canada

IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on the implications of this cytokine in asthma is lacking. IL-33 would be mainly expressed by structural cells, but whether proinflammatory cytokines modulate its expression in airway smooth muscle cells (ASMC) is unknown. Endobronchial biopsies were obtained from adults with mild (n = 8), moderate (n = 8), severe (n = 9), asthma and from control subjects (n = 5). Immunocytochemistry, laser-capture microdissection, reverse transcriptase, and real-time quantitative PCR were used for determining IL-33 expression in the lung tissues. ASMC isolated from resected lung specimens were cultured with proinflammatory cytokines and with dexamethasone. IL-33 expression by ASMC was determined by PCR, ELISA, and Western blotting. Higher levels of IL-33 transcripts are detected in biopsies from asthmatic compared with control subjects, and especially in subjects with severe asthma. ASMC show IL-33 expression at both protein and mRNA levels. IL-33 and TNF- transcript levels correlate in the lung tissues, and TNF- up-regulates IL-33 expression by cultured ASMC in a time- and dose-dependent manner. IFN- also increases IL-33 expression and shows synergistic effect with TNF-. Dexamethasone fails to abolish TNF--induced IL-33 up-regulation. IL-33 expression increases in bronchial biopsies from subjects with asthma compared with controls, as well as subjects with asthma severity. ASMC are a source of the IL-33 cytokine. Our data propose IL-33 as a novel inflammatory marker of severe and refractory asthma.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by the J. T. Costello Memorial Fund and the Richard and Edith Strauss Canada Foundation. Q.H. is a recipient of McGill University Health Center Strauss Chair in Respiratory Medicine. D.P. is a recipient of an doctoral studentship from the Fonds de la Recherche en Santé du Québec.

² Address correspondence and reprint requests to Dr. Qutayba Hamid, Meakins-Christie Laboratories, 3626 St. Urbain, Montreal, Quebec, Canada H2X 2P2. E-mail address: qutayba.hamid{at}mcgill.ca

³ Abbreviations used in this paper: ASMC, airway smooth muscle cell; DEX, dexamethasone 21-phosphate disodium salt; FEV₁, forced expiratory volume in 1 s; LCM, laser capture microdissection/microdissected; MMA, mithramycin A.

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The JI 2009 183: 4829-4830. [Full Text]