Clotrimazole inhibits lung fibroblast proliferation in vitro: implications for use in the prevention and treatment of obliterative bronchiolitis after lung transplantation.
BACKGROUND
Immunosuppressive therapy has limited activity against the mesenchymal cell proliferation of obliterative bronchiolitis. Clotrimazole (CLT) has been shown to inhibit proliferation in normal and cancer cell lines. Here we investigate whether CLT inhibits the proliferation of lung mesenchymal cells.


METHODS
Proliferation of human lung fibroblasts (MRC-5) in the presence of CLT was determined by [3H]thymidine incorporation. Messenger ribonucleic acid (mRNA) expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta after treatment with CLT was measured by reverse transcriptase-polymerase chain reaction.


RESULTS
Treatment of MRC-5 cells with CLT resulted in a significant reduction in proliferation as assessed by DNA incorporation and cell counts compared with dimethylsulfoxide alone. There was no cytotoxic effect associated with CLT treatment. Reverse transcriptase-polymerase chain reaction demonstrated a marked decrease in PDGF-B and TGF-beta mRNA levels in cells treated with CLT compared with those treated with dimethylsulfoxide.


CONCLUSIONS
CLT inhibits proliferation of human lung fibroblasts. This inhibitory effect is associated with decreased levels of PDGF-B and TGF-beta mRNA expression and may have value in the prevention and treatment of obliterative bronchiolitis.
Smith
M A
MA
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Zhang
W
W
Naziruddin
B
B
Cooper
J D
JD
Patterson
G A
GA
Mohanakumar
T
T
D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002860:Chromium Radioisotopes; D003022:Clotrimazole / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D016040:Lung Transplantation / Q000009:adverse effects
D002860:Chromium Radioisotopes; D006131:Growth Inhibitors; D003022:Clotrimazole