Investigation of the antifibrotic effect of IFN-γ on fibroblasts in a cell culture model of Peyronie's disease

Objective: A broad spectrum of options is available for treatment of Peyronie's disease; however, the effects of minimally invasive therapy are generally inadequate. Although useful, oral drugs must be administered at onset of the disease. only a few patients request penile surgery. Therefore, new medical treatments for Peyronie's disease are needed. A better understanding of the pathogenesis of Peyronie's disease is required to facilitate development of these new medical treatments. Several studies have described an increased level of TGF-beta in the fibrotic plaques of patients with Peyronie's disease, underscoring this important signalling pathway in the onset and/or development of Peyronie's disease. Methods: Plaque biopsies were taken from 16 patients with Peyronie's disease. Furthermore, 7 patients without Peyronie's disease were biopsied to provide control material. Fibroblasts were cultured from biopsy tissue, and cultured fibroblasts were stimulated with TGF-beta 1, BMP-2, IFN-gamma, and IFN-gamma combined with one of the other stimuli. Protein was extracted from treated fibroblasts and prepared for immunoblots. The membranes were probed for phosphorylated Smad and total Smad to indicate activation of TGF-beta signalling. Results: An agonistic effect of IFN-gamma on TGF-beta signalling was observed. Stimulation with TGF-beta 1 increased levels of phospho-Smad2 and phospho-Smad3. After stimulation with TGF-beta 1 and IFN-gamma combined, the levels of phospho-Smads were higher than those observed with stimulation with TGF-beta 1 alone. Conclusions: The profibrotic effect of TGF-beta 1 is enhanced by IFN-gamma in fibroblasts from patients with Peyronie's disease. The inhibitory effects of IFN-gamma on the TGFP pathway do not appear in Peyronie's disease. Therefore, IFN-gamma cannot be taken as a useful tool in the therapy of Peyronie's disease. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.