Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and TNF-alpha in vitro

BACKGROUND: Gingival overgrowth occurs in patients receiving nifedipine. Gingival inflammation may be an etiologic factor. METHODS: Gingival fibroblasts were either exposed to (i) 0-500 ng/ml TNF-alpha or 10(-7) M nifedipine or (ii) 0-500 ng/ml TNF-alpha + 10(-7) M nifedipine for 7 days. 3H-proline was used to quantify collagenous protein synthesis. RESULTS: Both TNF-alpha and 10(-7) M nifedipine significantly decreased cell proliferation, and 10(-7) M nifedipine + 500 ng/ml TNF-alpha reversed these effects. Collagenous protein synthesis was significantly reduced by TNF-alpha and was significantly enhanced by either 10(-7) M nifedipine or 5-500 ng/ml TNF-alpha + 10(-7) M nifedipine. CONCLUSIONS: Our data report that nifedipine reverses the primary effects of TNF-alpha on collagenous protein synthesis. Patients with gingivitis could be susceptible to gingival overgrowth during nifedipine therapy as a result of synergistic effects of these agents on fibroblast metabolism, which occurs irrespective of reduced cell numbers.