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IFN-gamma, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

Moynihan, BJ; Tolloczko, B; El Bassam, S; Ferraro, P; Michoud, MC; Martin, JG; Laberge, S (2008) IFN-gamma, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13. RESPIRATORY RESEARCH, 9 (84). ISSN 1465-9921
SGUL Authors: Moynihan, Barry

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Background: IL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6). The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM) cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13. Methods:Cultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine. Results:IL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression. Conclusion:Pre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine. The mechanism of IL-4 and IL-13 induced desensitization does not appear to involve either downregulation of receptor expression or induction of the IL-13Rα2 or the SOCS proteins.

Item Type: Article
Additional Information: © 2008 Moynihan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Calcium, Cell Proliferation, Cells, Cultured, Chemokine CCL11, Histamine, Humans, Interferon-gamma, Interleukin-13, Interleukin-13 Receptor alpha1 Subunit, Interleukin-13 Receptor alpha2 Subunit, Interleukin-4, Lung, Myocytes, Smooth Muscle, RNA, Messenger, Receptors, Interleukin-4, STAT6 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Science & Technology, Life Sciences & Biomedicine, Respiratory System, RESPIRATORY SYSTEM, RECEPTOR ALPHA-CHAIN, INTERFERON-GAMMA, GENE-EXPRESSION, SIGNAL-TRANSDUCTION, EPITHELIAL-CELLS, UP-REGULATION, EOSINOPHILIC INFLAMMATION, MUCUS PRODUCTION, EOTAXIN RELEASE, CUTTING EDGE, 1102 Cardiovascular Medicine And Haematology, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS)
Journal or Publication Title: RESPIRATORY RESEARCH
ISSN: 1465-9921
Related URLs:
30 December 2008Published
Web of Science ID: WOS:000263726200001
Publisher's version:

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