IMMUNOSUPPRESSION Do MMP-1 Levels of Gingival Fibroblasts Have a Role in the Gingiva Overgrowth of Cyclosporine-Treated Patients? S. Sonmez, C. Cavdar, C. Gunduz, N. Nizam, C. Biray, K. Atila, and T. Camsari ABSTRACT The aim of this study was to compare the matrix metalloproteinase-1 (MMP-1) levels in gingival fibroblast cultures derived from two groups of renal transplant patients receiving cyclosporine (CsA) who exhibit gingival overgrowth and who have healthy periodontium. Gingivalfibroblasts obtained from four patients with CsA-induced gingival overgrowth (CsA-GO) and four patientswho receive CsA buthave healthy periodontium were incubated with increasing concentrations of CsA and cultured for 72 hours. Expression levels of MMP-1 in all the groups were measured four times at 0, 24, 48, and 72 hours by the Rapid Collagenase Assay Kit. No significant difference was seen at baseline. As the CsA concentration and the duration in the cell media increased, the CsA-GO showed that fibroblasts displayed significantly suppressed MMP-1 levels with respect to the baseline, at which fibroblasts from CsA patients with healthy periodontium exhibited the same result as at the highest CsA concentration. Results of this study indicated that CsA therapy did not have a significanteffecton MMP-1 levels.Since the overall pathogenesis of drug-induced gingival hyperplasia has been accepted as multifactorial, down-regulation of MMP-1 expression may play a minor role. B IOCHEMICAL events in the developmentof the gingival overgrowth(GO) associatedwith CsA treatment (CsA-GO) are not well understood at present. They are probably a consequence of disturbance in the homeostatic equilibrium between synthesis and degrada- tion of extracellular matrix (ECM) molecules or interfer- ence in fibroblast-proliferation rates. 1,2 In the susceptible patient, GO usually develops within 1 to 3 months 2,3 after initiation of CsA therapy.The overall incidence is ap- proximately 25% to 30%. 3,4 An importantregulator of connective tissue remodeling, MMP-1 is present in high concentrations, especially in inflamed gingival regions, including those affected with periodontal disease. 5 The collagen turnover in gingival tissues promoted by fibro- blasts occurs in two ways: the phagocytic pathway and the From Ege University, Schoolof Dentistry, Department of Peri- odontology; Dokuzeylul University, School of Medicine, Depart- ment of Nephrology;Ege University,School of Medicine,De- partment of Medical Biology, and Dokuzeylul University, School of Medicine, Department of General Surgery, Izmir, Turkey. This work was supported by the Ege University Research Foundation. Address reprintrequests to Sule Sonmez,Ege University, School of Dentistry,Departmentof Periodontology,Bornova 35100, Izmir, Turkey. E-mail: sule.sonmez@ege.edu.tr © 2008 by Elsevier Inc. All rights reserved. 0041-1345/08/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2007.11.064 Transplantation Proceedings, 40, 181–183 (2008) 181