In Normal Human Lung Fibroblasts, Cigarette Smoke Extract Induces a Reversible Multi-Phase Cell Cycle Arrest

In Normal Human Lung Fibroblasts, Cigarette Smoke Extract Induces a Reversible Multi-Phase Cell Cycle Arrest Author(s): G. Costanzo, C. D'Anna, R. Di Giorgi, D. Cigna, G. Bonsignore, A.M. Vignola IBIM CNR, Palermo, Italy; Institute of Pneumology and Medicine, University, Palermo, Italy Cigarette smoking is the major risk factor for pulmonary diseases, such as COPD, asthma and lung cancer. Among the different toxic effects of cigarette smoke on human tissue, oxidation of structural and functional molecules and modulation of cell turnover play a major role. Recent evidences indicate that the pulmonary fibroblast can contribute directly to pulmonary inflammation and ultimately to airway wall remodelling. To defend against the potential damage induced by reactive oxygen species (ROS), proliferating cells enter a transient cell cycle arrest. We treated human lung fibroblasts (HFL-1) with cigarette smoke extract (CSE10% for 24h). We found that CSE induced a reversible multi-phase cell cycle arrest at the G1, S and G2/M phase. The DNA ladder analysis showed that HFL-1 cells were not in apoptosis. To investigate if CSE treatment induced an inflammatory response, we assessed the expression of two MAP kinases, ERK and p38, by western blot analysis. We found that CSE increases both ERK-P and p38-P, suggesting that these molecules mediate the CSE inflammatory effects. These results provide evidences that: 1) CSE treatment induces an oxidative stress which leads to a reversible cell cycle arrest; 2) CSE produces an inflammatory phenotype through a cross-talk between MAPKs. Wednesday, May 26, 2004 8:15 AM