Tobacco smoke reduces viability in human lung fibroblasts: protective effect of glutathione S-transferase P1.
Cigarette smoking is thought to be a major risk factor in various lung diseases including lung cancer and emphysema. However, the direct effect of cigarette smoke on the viability of lung-derived cells has not been fully elucidated. In this study, we investigated the viability of human lung fibroblast-derived (HFL1) cells to different concentrations of cigarette smoke extract (CSE). CSE induced apoptosis at lower concentrations (10-25%) and necrosis at higher concentrations (50-100%). We also examined the effects of glutathione S-transferase P1 (GSTP1), one of the xenobiotic metabolizing and antioxidant enzymes in the lung, against the cytotoxicity of CSE. Our results indicated that the level of HFL1 cell death was decreased by transfection with a GSTP1 expression vector and was increased by GSTP1 antisense vector transfection. Therefore, transient overexpression and underexpression of GSTP1 appeared to inhibit and enhance the cytotoxic effects of CSE on HFL1 cells, suggesting that GSTP1 may have protective effects against cigarette smoke in the airway cells.
Ishii
T
T
Department of Geriatric Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Matsuse
T
T
Igarashi
H
H
Masuda
M
M
Teramoto
S
S
Ouchi
Y
Y
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D008168:Lung / Q000166:cytology*; D009336:Necrosis; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D012996:Solutions; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014162:Transfection
D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D012996:Solutions; D014028:Tobacco Smoke Pollution; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase