Cigarette smoke-induced kinin B1 receptor promotes NADPH oxidase activity in cultured human alveolar epithelial cells
| Autor: | André Morin, Karim Lahjouji, James Chi-Jen Lin, Réjean Couture, Jean-Philippe Roy, Sébastien Talbot, Jacques Sénécal |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Receptor
Bradykinin B2 Physiology Interleukin-1beta Gene Expression Pharmacology Receptor Bradykinin B1 Biochemistry Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Superoxides Smoke Bradykinin B2 Receptor Antagonists medicine Humans Enzyme Inhibitors Cells Cultured A549 cell Inflammation Oxidase test NADPH oxidase biology Superoxide Tumor Necrosis Factor-alpha Niflumic acid Smoking NF-kappa B NADPH Oxidases Epithelial Cells Kinin Bradykinin B1 Receptor Antagonists Enzyme Activation Pulmonary Alveoli Oxidative Stress chemistry Cyclooxygenase 2 Apocynin biology.protein Cyclooxygenase 1 Tumor necrosis factor alpha Particulate Matter medicine.drug Signal Transduction |
| Zdroj: | Peptides. 32(7) |
| ISSN: | 1873-5169 |
| Popis: | Pulmonary inflammation is an important pathological feature of tobacco smoke-related lung diseases. Kinin B1 receptor (B1R) is up-regulated in the rat trachea chronically exposed to cigarette-smoke. This study aimed at determining (1) whether exposure to total particulate matter of the cigarette smoke (TPM) can induce B1R in human alveolar epithelial A549 cells, (2) the mechanism of B1R induction, (3) the functionality of de novo synthesized B1R, and (4) the role of B1R in TPM-induced increase of superoxide anion (O₂(●⁻)) level. Results show that A549 cells exposed to 10 μg/ml TPM increased O₂(●⁻) level along with B1R (protein and mRNA) and IL-1β mRNA. In contrast, B2R and TNF-α mRNA were not affected by TPM. The increasing effect of TPM on O₂(●⁻) level was not significantly affected by the B1R antagonist SSR240612. TPM-increased B1R mRNA was prevented by co-treatments with N-acetyl-l-cysteine (potent antioxidant), diphenyleneiodonium (NADPH oxidase inhibitor), IL-1Ra (interleukin-1R antagonist) and SN-50 (specific inhibitor of NF-kB activation) but not by pentoxifylline (TNF-α release inhibitor), indomethacin and niflumic acid (COX-1 and -2 inhibitors). Stimulation of B1R with a selective agonist (des-Arg⁹-BK, 10 μM; 30 min) increased O₂(●⁻)production which was prevented by apocynin and diphenyleneiodonium (NADPH oxidase inhibitors). Data suggest that the increased expression of B1R by TPM in A549 cells is mediated by oxidative stress, IL-1β and NF-kB but not by cyclooxygenases or TNF-α. The amplification of O₂(●⁻) levels via the activation of B1R-NADPH oxidase may exacerbate pulmonary inflammation and contribute to the chronicity of tobacco smoke-related lung diseases. |
| Databáze: | OpenAIRE |
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