IFN-gamma, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13
| العنوان: | IFN-gamma, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13 |
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| المؤلفون: | Barry J. Moynihan, Sophie Laberge, Pascale Ferraro, Marie-Claire Michoud, James G. Martin, Barbara Tolloczko, Souad El Bassam |
| المصدر: | Respiratory Research Respiratory Research, Vol 9, Iss 1, p 84 (2008) |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Eotaxin, Chemokine CCL11, Receptor complex, Receptor expression, medicine.medical_treatment, Myocytes, Smooth Muscle, Suppressor of Cytokine Signaling Proteins, Biology, 03 medical and health sciences, chemistry.chemical_compound, Interferon-gamma, 0302 clinical medicine, Suppressor of Cytokine Signaling 1 Protein, Downregulation and upregulation, medicine, Humans, RNA, Messenger, Lung, Interleukin 4, Cells, Cultured, 030304 developmental biology, Cell Proliferation, lcsh:RC705-779, 0303 health sciences, Interleukin-13, Research, lcsh:Diseases of the respiratory system, Molecular biology, Interleukin-13 Receptor alpha1 Subunit, 3. Good health, Receptors, Interleukin-4, Cytokine, chemistry, Suppressor of Cytokine Signaling 3 Protein, Interleukin 13, Interleukin-13 Receptor alpha2 Subunit, Calcium, Interleukin-4, STAT6 Transcription Factor, Histamine, 030215 immunology |
| الوصف: | BackgroundIL-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.MethodsCultured 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.ResultsIL-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.ConclusionPre-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. |
| تدمد: | 1465-993X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2c81423398c6fa937cad6dea21c893dTest https://pubmed.ncbi.nlm.nih.gov/19116009Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e2c81423398c6fa937cad6dea21c893d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1465993X |
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