The effect of IL-l.ALPHA. and nifedipine of cell proliferation and DNA synthesis in cultured human gingival fibroblasts

Abstract

The effect of nifedipine and interleukin-α (IL-1α) on the cell proliferation and DNA synthesis was studied in human gingival fibroblasts derived from 5 patients who developed gingival overgrowth (nifedipine responders) and 5 patients who did not develop gingival overgrowth (nifedipine non-responders) in response to nifedipine. Epidermal growth factor was used as a positive control. The fibroblasts derived from nifedipine responders tended to have a numerically greater rate of cell proliferation and DNA synthesis ( 3 H-thymidine incorporation) than those from nifedipine nonresponders in the presence of nifedipine and IL-1α. Fibroblasts derived from nifedipine responders showed significantly higher cell proliferation rate in the presence of nifedipine and IL-1α, than nifedipine or IL-1α alone on both the second and the fourth day of incubation (P < 0.05). A combination of IL-1α and epidermal growth factor also showed significantly greater cell proliferation than IL-1α alone on the second day (P < 0.05). The DNA synthesis rate with a combination of nifedipine and IL-1α was higher than that for nifedipine alone on the second day (P < 0.01), and IL-1α alone on the fourth day (P < 0.05) in gingival fibroblasts originating from nifedipine responders. These results suggest that the interaction between nifedipine and gingival inflammation might play an important role in the pathogenesis of nifedipine-induced gingival overgrowth. (J. Oral Sci. 47, [105][106][107][108][109][110] 2005)

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

“…Additionally, nifedipine more than amlodipine stimulated (cardiac) fibroblasts [32], which was undesired in that case but hopeful for wound healing. A similar stimulatory effect of nifedipine was observed in patients who had developed a gingiva hyperplasia after long-term intake [12, 33]. However, in gingiva fibroblasts the influence on the collagen matrix dominated.…”

“…Especially timolol exerted a pro-proliferative effect after local application [8]. Bhaskar et al [11] demonstrated that the calcium channel blocker amlodipine enhances the tensile strength of wounds, but not the epithelialization [12, 13]. In contrast to these rather beneficial effects, angiotensin-converting enzyme (ACE) blockers affected proliferation and migration of skin cells negatively [14, 15].…”

Stimulation of Cells Derived from Nifedipine-induced Gingival Overgrowth with Porphyromonas gingivalis, Lipopolysaccharide, and Interleukin-1β

“…In the present study, the unique hyper-responsiveness of androgen receptor mRNA levels in response to IL-1␤ in nifedipine-induced gingival overgrowth cells may explain the link between the stimulatory effect of pro-inflammatory cytokine, elevated levels of adrenal androgen, and increased repair potential in nifedipine-induced gingival overgrowth fibroblasts. It was also shown that IL-1␣, a potent IL-1␤ analogue, exerted a synergistic effect with nifedipine on cell proliferation and DNA synthesis in cultured human gingival fibroblasts (Sato et al, 2005). We propose that this pro-inflammatory cytokine plays a major role in modulating soft-tissue enlargement in nifedipine-induced gingival overgrowth.…”

Differences of Cell Growth and Cell Cycle Regulators Induced by Basic Fibroblast Growth Factor Between Nifedipine Responders and Non-responders

“…IL-1 has been reported to be a potential regulator of fibroblast proliferation (10 -12), with significantly higher levels found in the gingival crevicular fluid of patients with periodontal disease (13,14). We have previously shown that a mixture of nifedipine and IL-1α increased cell proliferation, suggesting that IL-1α may be a co-factor for nifedipine-induced gingival overgrowth (15,16). We have also demonstrated that IL-1α, but not nifedipine, accelerates the formation of intercellular basic fibroblast growth factor (bFGF) in cultured human gingival fibroblasts (17).…”