フェニトイン誘発性歯肉増殖症発症に関与するコラーゲン代謝機構の解析

抄録

Gingival overgrowth is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT-induced gingival overgrowth characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF) . PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP-1 and α2 β1 integrin mediated endocytosis. These synergistic effects may cause collagen accumulation, leading to gingival overgrowth. It has also been reported that dental plaque is the most important factor to enhance deterioration caused by PHT-induced gingival overgrowth and low concentrations of TNF-α were found in chronically inflamed sites. We examined the synergistic effect of PHT and TNF-α on collagen metabolism in HGF. TNF-α and PHT together cause impaired collagen metabolism by suppression of enzymatic degradation via TIMP-1 upregulation and integrin-mediated endocytosis. These synergistic effects may also be involved in TNF-α-and PHT-induced severe gingival overgrowth.