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 mese nchymal 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 mesenchy mal cells. Methods. Proliferation of human lung fibroblasts (MRC-5) in the presence of CLT was determined by [H-3]thymidine incorporation. Messenger ribonucleic acid (mRNA) expression of platelet-derived growth factor (PDGF)-B and trans forming growth factor (TGF)-beta after treatment with CLT was measured by r everse transcriptase-polymerase chain reaction. Results. Treatment of MRC-B cells with CLT resulted in a significant reduct ion in proliferation as assessed by DNA incorporation and cell counts compa red with dimethylsulfoxide alone. There was no cytotoxic effect associated with CLT treatment. Reverse transcriptase-polymerase chain reaction demonst rated a marked decrease in PDGF-B and TGF-beta mRNA levels in cells treated with CLT compared with those treated with dimethylsulfoxide. Conclusion. CLT inhibits proliferation of human lung fibroblasts. This inhi bitory effect is associated with decreased levels of PDGF-B and TGF-P mRNA expression and may have value in the prevention and treatment of obliterati ve bronchiolitis.