Glutathione prevents inhibition of fibroblast-mediated collagen gel contraction by cigarette smoke

Hui Jung Kim, Xiangde Liu, Hangjun Wang, Tadashi Kohyama, Tetsu Kobayashi, Fu Qiang Wen, Debra J. Romberger, Shinji Abe, William MacNee, Irfan Rahman, Stephen I. Rennard

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Cigarette smoke, the major risk factor for the development of emphysema, contains over 4,700 chemical compounds, including free radicals and other oxidants (1014/puff). An imbalance between oxidants and antioxidants has been proposed in the pathogenesis of chronic obstructive pulmonary disease. Inhibition of repair processes has been suggested to be one pathway contributing to the development of emphysema. We hypothesized that cigarette smoke inhibition of repair might result from a shift of the oxidant/antioxidant balance in favor of oxidants. To evaluate this hypothesis, N-acetyl-L-cysteine (NAC), which serves as a substrate for glutathione (GSH) production, and buthionine sulfoximine (BSO), which inhibits GSH production, were incubated in the presence and absence of cigarette smoke extract (CSE) with fibroblasts in three-dimensional collagen gels. Neither agent alone altered gel contraction. CSE inhibition of gel contraction, however, was mitigated by NAC and potentiated by BSO. Parallel effects were observed on cigarette smoke inhibition of fibronectin production and mRNA expression as well as by changes in intracellular GSH content. Pretreatment of fibroblasts with NAC or BSO resulted in similar effects, suggesting that neither agent was acting directly on smoke but, rather, was altering cellular response to smoke. In conclusion, smoke inhibition of fibroblast repair, as reflected by collagen gel contraction and fibronectin production, may be modulated by intracellular GSH levels.

Original languageEnglish (US)
Pages (from-to)L409-L417
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number2 27-2
StatePublished - Aug 3 2002

Keywords

  • Chronic obstructive pulmonary disease
  • Oxidants

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Kim, H. J., Liu, X., Wang, H., Kohyama, T., Kobayashi, T., Wen, F. Q., Romberger, D. J., Abe, S., MacNee, W., Rahman, I., & Rennard, S. I. (2002). Glutathione prevents inhibition of fibroblast-mediated collagen gel contraction by cigarette smoke. American Journal of Physiology - Lung Cellular and Molecular Physiology, 283(2 27-2), L409-L417.