Lu H-K, Tseng C-C, Lee Y-H, Li C-L, Wang L-F. Flutamide inhibits nifedipine- and interleukin-1β-induced collagen overproduction in gingival fibroblasts. J Periodont Res 2010; 45: 451-457. © 2010 John Wiley & Sons A/S Background and Objective: To understand the role of the androgen receptor in gingival overgrowth, the effects of flutamide on interleukin-1β- and nifedipine-induced gene expression of connective tissue growth factor (CTGF/CCN2) and collagen production in gingival fibroblasts were examined. Material and Methods: Gingival fibroblasts from healthy subjects and patients with dihydropyridine-induced gingival overgrowth (DIGO) were used. Confluent cells were treated with nifedipine, interleukin-1β or both. The mRNA expression was examined using real-time polymerase chain reaction, and the concentration of total soluble collagen in conditioned media was analysed by Sircol Collagen Assay. In addition, the protein expressions of androgen receptor, CTGF/CCN2 and type I collagen in gingival tissue were determined by western blot. Results: Interleukin-1β was more potent than nifedipine in stimulating CTGF/CCN2 and procollagen α1(I) mRNA expression, and there was an additive effect of the two drugs. Healthy cells exhibited an equal or stronger response of procollagen α1(I) than those with DIGO, but DIGO cells displayed a stronger response in the secretion of soluble collagen in the same conditions. Flutamide, an androgen receptor antagonist, inhibited stimulation by nifedipine or interleukin-1β. Additionally, the protein expressions of androgen receptor and type I collagen were higher in DIGO gingival tissue than those in healthy gingival tissue. Conclusion: The data suggest that both nifedipine and interleukin-1β play an important role in DIGO via androgen receptor upregulation and that gingival overgrowth is mainly due to collagen accumulation. Flutamide decreases the gene expression and protein production of collagen from dihydropyridine-induced overgrowth cells. © 2010 John Wiley & Sons A/S.
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