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Interleukin-4 Promotes Airway Remodeling in Asthma*: Regulation of Procollagen I (α1) Gene by Interleukin-4

Céline Bergeron, MD; Nathalie Pagé, BSc; Benoit Barbeau, PhD; Jamila Chakir, PhD
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*From the Centre de recherche (Drs. Bergeron and Chakir, and Ms. Pagé), Hôpital Laval, Institut universitaire de cardiologie et de pneumologie, Sainte-Foy, Québec; and Centre de recherche en infectiologie (Dr. Barbeau), CHUQ-Pavillon CHUL, Université Laval, Sainte-Foy, Québec, Canada.

Correspondence to: Jamila Chakir, PhD, Centre de recherche, Hôpital Laval, 2725 Chemin Sainte-Foy, Sainte-Foy, Québec, Canada, G1V 4G5; e-mail: jamila.chakir@med.ulaval.ca



Chest. 2003;123(3_suppl):424S. doi:10.1378/chest.123.3_suppl.424S
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In bronchial mucosa, T cells are in close association with stromal cells. This intimate cell contact raises the possibility of cross-talk between the two cell types through cytokines. Studies with animal models have revealed significant effects of interleukin (IL)-4 on the structural cells of the airways. We herein present the first human study, investigating the profibrotic effect of IL-4 in asthma. We postulated that IL-4 may modulate type I collagen synthesis and degradation during the injury-repair cycle of asthma. Bronchial fibroblasts from asthmatics and healthy control subjects were incubated in the presence of IL-4 (5 ng/mL) for up to 24 h. We then measured procollagen I, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-2 production and gene expression. The effect of IL-4 on regulation of collagen I (α1) promoter was studied through transient cell transfections. We found that IL-4 significantly stimulated the production and gene expression of procollagen I (α1) by bronchial fibroblasts. In transient transfection experiments, IL-4 increased promoter activity by threefold. IL-4 decreased MMP-2 production and activity and did not alter TIMP-2 production. In conclusion, human IL-4 positively regulates procollagen I (α1) transcription by direct promoter activation and increases the TIMP-2/MMP-2 ratio, thereby supporting the profibrotic effect of this cytokine in asthma. This study emphasizes that IL-4 could be a potential target for future therapeutic approaches in asthmatic patients.

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