Cigarette smoke-induced kinin B1 receptor promotes NADPH oxidase activity in cultured human alveolar epithelial cells

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2011-07, Vol.32 (7), p.1447-1456
• Main Authors: Talbot, Sébastien, Lin, James Chi-Jen, Lahjouji, Karim, Roy, Jean-Philippe, Sénécal, Jacques, Morin, André, Couture, Réjean
• Format: Article
• Language: English
• Subjects: acetylcysteine; Activation; agonists; antagonists; antioxidants; Biological and medical sciences; Bradykinin B1 Receptor Antagonists; Bradykinin B2 Receptor Antagonists; Cells, Cultured; chronic exposure; Cigarette smoke; Cigarettes; Cyclooxygenase 1 - genetics; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Diseases; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Humans; indomethacin; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Inhibitors; Interleukin-1 β; interleukin-1beta; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Kinin B1 receptor; Lungs; Medical sciences; messenger RNA; NAD(P)H oxidase (H2O2-forming); NADP (coenzyme); NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - metabolism; Oxidase; oxidases; Oxidative stress; Oxidative Stress - drug effects; oxygen; Particulate Matter - adverse effects; Particulate Matter - pharmacology; particulates; pentoxifylline; pneumonia; prostaglandin synthase; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - immunology; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; rats; Receptor, Bradykinin B1 - genetics; Receptor, Bradykinin B1 - metabolism; Receptor, Bradykinin B2 - genetics; Receptor, Bradykinin B2 - metabolism; Receptors; Signal Transduction - drug effects; Smoke - adverse effects; smokes; Smoking - adverse effects; superoxide anion; Superoxides - analysis; Superoxides - metabolism; Tobacco; Tobacco smoke; Tobacco, tobacco smoking; Toxicology; transcription factor NF-kappa B; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: endocrinology
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2011.05.005

► Upregulation of kinin B1 receptor (B1R) and interleukin-1β. ► Enhanced superoxide anion production. ► Prevention of B1R induction and oxidative stress by NADPH oxidase inhibitors. ► Enhanced superoxide anion production by B1R activation. 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 10μg/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, 10μM; 30min) 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.