The effects of leptin on airway smooth muscle responses
| Autor: | Adrian Fanat, Parameswaran Nair, P. Gerard Cox, Luke J. Janssen, Katherine Radford, Marc Peters-Golden |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Leptin medicine.medical_specialty medicine.medical_treatment Clinical Biochemistry Myocytes Smooth Muscle Dinoprostone Proinflammatory cytokine Internal medicine medicine Animals Humans Molecular Biology Lung Cells Cultured Cell Proliferation Platelet-Derived Growth Factor Leptin receptor biology Chemistry Growth factor Cell Biology Recombinant Proteins Blot Enzyme Activation Cytokine Endocrinology biology.protein Cattle Platelet-derived growth factor receptor Proto-oncogene tyrosine-protein kinase Src Muscle Contraction Signal Transduction |
| Zdroj: | American journal of respiratory cell and molecular biology. 39(4) |
| ISSN: | 1535-4989 |
| Popis: | Obesity is associated with asthma and airway hyperresponsiveness. Leptin modulates some of the proinflammatory effects observed in obesity. The objective of this study was to determine the effects of leptin on airway smooth muscle responses. The effect of leptin (0.1-100 ng/ml) on migration (toward platelet-derived growth factor [PDGF], 10 ng/ml, across collagen-coated membrane in Transwell culture plates), proliferation (by BrDU incorporation), and cytokine production (by Bioplex bead assay) of cultured human airway smooth muscle cells from nine nonasthmatic donors was assessed. Effects of leptin on the contractile responses were studied in bovine tracheal smooth muscle rings. Leptin receptor expression and activation of STAT-3, Src kinase, Suppressor of Cytokine Signaling-3 (SOCS-3), and COX were evaluated by Western blotting and PCR. PGE(2) levels in supernatant were assessed by enzyme immunoassay. Human airway smooth muscle cells express leptin receptor, which, when engaged, phosphorylated STAT-3. Leptin inhibited PDGF-induced human airway smooth muscle migration and proliferation and IL-13-induced eotaxin production. Leptin did not stimulate cytokine synthesis and did not evoke contractile responses or inhibit isoproterenol-induced relaxation of carbachol-induced contraction of bovine tracheal rings. The inhibitory effects on migration and eotaxin production are not due to activation of SOCS-3 but are partly due to increased production of PGE(2) because they were attenuated by indomethacin. In conclusion, leptin inhibited human airway smooth muscle proliferation, migration toward PDGF, and IL-13-induced eotaxin production. This is partly mediated by PGE(2) secretion from smooth muscle cells induced by leptin. The association between obesity and asthma is unlikely to be due to a direct effect of leptin on airway smooth muscle. |
| Databáze: | OpenAIRE |
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