Investigation of the antifibrotic effect of IFN-gamma 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-beta1, 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-beta1 increased levels of phospho-Smad2 and phospho-Smad3. After stimulation with TGF-beta1 and IFN-gamma combined, the levels of phospho-Smads were higher than those observed with stimulation withTGF-beta1 alone.


CONCLUSIONS
The profibrotic effect of TGF-beta1 is enhanced by IFN-gamma in fibroblasts from patients with Peyronie's disease. The inhibitory effects of IFN-gamma on the TGF-beta 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.
Haag
Simone M
SM
Department of Urology and Pediatric Urology, Justus Liebig University Giessen, Giessen, Germany.
Hauck
Ekkehard W
EW
Eickelberg
Oliver
O
Szardening-Kirchner
Carolin
C
Diemer
Thorsten
T
Weidner
Wolfgang
W
D001706:Biopsy; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010411:Penile Induration / Q000188:drug therapy*; D010766:Phosphorylation; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma