title: Effect of cigarette smoke on fibroblast-mediated gel contraction is dependent on cell density.
abstract: 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)-beta1, fibronectin, PGE(2), and TGF-beta1 mRNA were quantified. Although both 5 and 10% CSE inhibited contraction by low-density fibroblasts (1 x 10(5) cell/ml), only 5% CSE augmented contraction in higher-density cultures (3-5 x 10(5) cells/ml). CSE also inhibited fibronectin and TGF-beta1 production in low-density cultures but stimulated fibronectin production in high-density cultures. Active TGF-beta1 was readily detectable only in higher-density cultures and was markedly augmented by 5% CSE. In contrast, although TGF-beta1 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-beta1. These effects may help explain the varied pathologies associated with exposure to cigarette smoke.
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Hangjun
authors.initials: H
authors.lastname: Wang
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Umino
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
authors.forename: Yun Kui
authors.initials: YK
authors.lastname: Zhu
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Wen
authors.forename: John R
authors.initials: JR
authors.lastname: Spurzem
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Romberger
authors.forename: Hui Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000502:physiology*; D005353:Fibronectins / Q000096:biosynthesis; D005782:Gels; D006801:Humans; D008168:Lung / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1
chemical_list: D000906:Antibodies; D005353:Fibronectins; D005782:Gels; D012333:RNA, Messenger; D012906:Smoke; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D015232:Dinoprostone