Differential activation of MAP kinase signaling pathways and nuclear factor-kappaB in bronchoalveolar cells of smokers and nonsmokers
| Autor: | K, Mochida-Nishimura, K, Surewicz, J V, Cross, R, Hejal, D, Templeton, E A, Rich, Z, Toossi |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Lipopolysaccharides Base Sequence Dose-Response Relationship Drug MAP Kinase Signaling System Smoking NF-kappa B Bronchi DNA-Binding Proteins Enzyme Activation Pulmonary Alveoli NF-KappaB Inhibitor alpha Case-Control Studies Humans I-kappa B Proteins Mitogen-Activated Protein Kinases DNA Probes Research Article |
| Zdroj: | Molecular medicine (Cambridge, Mass.). 7(3) |
| ISSN: | 1076-1551 |
| Popis: | BACKGROUND: Prolonged exposure of alveolar macrophages (AM) to components of tobacco smoke, including nicotine and aromatic hydrocarbons, may lead to alterations in activation of cellular signaling pathways. In this study, we compared the spontaneous and LPS-stimulated activation of MAP kinases and NF-kappaB in bronchoalveolar cells (BAC) from smokers and nonsmokers. MATERIAL AND METHODS: BAC, which were predominantly comprised of AM, were obtained by bronchoalveolar lavage of healthy volunteering adult smokers and nonsmokers. Nuclear and cytoplasmic extracts were prepared from cell lysates. Activation of NF-kappaB was assessed by electrophoretic mobility shift assay. Degradation of the inhibitor of NF-kappaB (IkappaB) and total MAP kinases were assessed by Western blot analysis. Activation of MAP kinases, ERK, SAPK/JNK, and p38 were assessed by immunoprecipitation of cell lysates and kinase assays. RESULTS: LPS induced the activation of NF-kappaB in a dose-dependent manner, but BAC from smokers were approximately 10 times more sensitive, and showed faster kinetics of activation of NF-kappaB than BAC from nonsmokers. All three classes of MAP kinase-ERK, SAPK, and p38-were simultaneously activated by LPS in BAC from smokers and nonsmokers. However, the individual MAP kinases exhibited differential kinetics of activation. Activation of p38 was more rapid in BAC from smokers, whereas the activation of ERK and SAPK was similar in both groups. CONCLUSION: The differences in activation of NF-kappaB and MAP kinases in BAC from smokers and nonsmokers may relate to the differences in their microenvironment in situ as affected by chronic exposure to cigarette smoke. These differences may contribute to the increased susceptibility of smokers to infections, including infection with HIV-1, and lung disease. |
| Databáze: | OpenAIRE |
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