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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 https://doi.org/10.1186/1465-9921-9-84
SGUL Authors: Moynihan, Barry

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Abstract

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 (http://creativecommons.org/licenses/by/2.0), 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:
Dates:
DateEvent
30 December 2008Published
Web of Science ID: WOS:000263726200001
URI: https://openaccess.sgul.ac.uk/id/eprint/107173
Publisher's version: https://doi.org/10.1186/1465-9921-9-84

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