Clotrimazole inhibits lung fibroblast proliferation in vitro: Implications for use in the prevention and treatment of obliterative bronchiolitis after lung transplantation

Michael A. Smith, Wanjiang Zhang, Bashoo Naziruddin, Joel D. Cooper, G. Alexander Patterson, T. Mohanakumar

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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)-β 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-β mRNA levels in cells treated with CLT compared with those treated with dimethylsulfoxide. Conclusion. CLT inhibits proliferation of human lung fibroblasts. This inhibitory effect is associated with decreased levels of PDGF-B and TGF-β mRNA expression and may have value in the prevention and treatment of obliterative bronchiolitis.

Original languageEnglish
Pages (from-to)1263-1267
Number of pages5
JournalTransplantation
Volume70
Issue number8
DOIs
StatePublished - Oct 27 2000

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