Effect of cigarette smoke on fibroblast-mediated gel contraction is dependent on cell density.
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.
Wang
Hangjun
H
Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
Liu
Xiangde
X
Umino
Takeshi
T
Kohyama
Tadashi
T
Zhu
Yun Kui
YK
Wen
Fu-Qiang
FQ
Spurzem
John R
JR
Romberger
Debra J
DJ
Kim
Hui Jung
HJ
Rennard
Stephen I
SI
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
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