Synergistic enhancement of collagenous protein synthesis by human gingivalfibroblasts exposed to nifedipine and interleukin-1-beta in vitro

Gingival overgrowth commonly occurs coincident to therapy with calcium chan nel blockers. The biologic mechanism for this condition is unknown; however , many clinicians suggest that poor oral hygiene may contribute to developm ent of the overgrowth. This study tests the hypothesis that collagenous pro tein synthesis by gingival fibroblasts is synergistically enhanced when the y are exposed to both nifedipine (N) and the pro-inflammatory cytokine, int erleukin-1-beta, a cytokine expressed in inflamed gingiva. Human gingival f ibroblasts were isolated from biopsies of normal gingiva and cells separate d into two groups. Group 1 was exposed to media containing 0, 5, 50, or 500 pg/ml IL-1-beta, or 10(-7) M N for 7 days; Group 2 was exposed to those co ncentrations of IL-1-beta + 10(-7) M N. [H-3]-proline was added to the medi um for the final 24 h. Cells and matrix were harvested and radioactivity de termined by liquid scintillation analysis. Means (d.p.m./10(3) cells) were compared by factorial ANOVA and Scheffe comparisons. Collagenous protein sy nthesis was significantly reduced by 5 pg/ml IL-1-beta + 10(-7) M N and enh anced by 500 pg/ml IL-1-beta + 10(-7) M N as compared to N or IL-1-beta alo ne. Thus, patients may be more susceptible to gingival overgrowth coinciden t to nifedipine therapy as a result of the synergistic enhancement of conne ctive tissue synthesis by these agents.