Effect of cigarette smoke on fibroblast-mediated gel contraction is dependent on cell density

1 Mount Sinai Hospital, Toronto, Canada M5G 1X5; 2 University of Nebraska Medical Center, Omaha, Nebraska 68198; 3 Pulmonary Medicine, Tokyo Medical and Dental University, Tokyo 113-8519; 4 Department of Respiratory Medicine, University of Tokyo, Tokyo 113-8655, Japan; 5 Department of Respiratory Diseases, Jincheng Hospital, Lanzhou 730050, China; and 6 Department of Internal Medicine, Seoul Adventist Hospital, Seoul 130-650, Korea Cigarette smoke exposure has been associated with a variety of diseases, including emphysema. The current study evaluated the interaction of cell density and cigarette smoke extract (CSE) on fibroblast contraction of collagen gels. Protein levels of transforming growth factor (TGF)- 1, fibronectin, PGE 2 , and TGF- 1 mRNA were quantified. Although both 5 and 10% CSE inhibited contraction by low-density fibroblasts (1 × 10 5 cell/ml), only 5% CSE augmented contraction in higher-density cultures (3-5 × 10 5 cells/ml). CSE also inhibited fibronectin and TGF- 1 production in low-density cultures but stimulated fibronectin production in high-density cultures. Active TGF- 1 was readily detectable only in higher-density cultures and was markedly augmented by 5% CSE. In contrast, although TGF- 1 mRNA expression was inhibited in high-density cultures by 10% CSE, expression was increased in the presence of 5% CSE. These results suggest that CSE-induced inhibition of low-density fibroblast contraction is due to inhibition of fibronectin production, whereas CSE's stimulatory effect on high-density cells is the result of increased release of TGF- 1. These effects may help explain the varied pathologies associated with exposure to cigarette smoke. cigarette smoke extract; collagen gels; transforming growth factor- ; lung