<原著>角膜実質細胞によるコラーゲン分解の調節機序について
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概要
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Excessive degradation of stromal collagen fibrils occurs in corneal ulceration. Keratocytes (corneal fibroblasts) seem to play a primary role in collagen degradation in corneal ulceration. However, the mechanisms of collagen degradation in corneal ulceration have not been fully understood. To understand the pathobiology of corneal ulceration, I developed a new in-vitro model in which keratocytes were cultured in a collagen matrix three dimensionally. Using this model, I searched for any factors which might regulate collagen degradation by keratocytes. Collagen degradation was measured by the amount of hydroxyproline in the hydrolysate. Collagen degradation by keratocytes depended on the number of cells, the concentration of collagen and the period of incubation. Among various cytokines and growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor 1 (IGF-1), interleukin 1 (IL-1) and interleukin 6 (IL-6) only IL-1 was found to enhance collagen degradation by keratocytes in a dose dependent manner. Interleukin 1 receptor antagonist (IL-1ra) antagonized the stimulatory effect of IL-1 on collagen degradation by keratocytes. IL-1 also stimulated collagenase synthesis by keratocytes. When phagocytic activity or intracellular lysosomal enzyme activities were inhibited by the addition of cytochalasin B or chloroquine, collagen degradation showed a decrease in the presence of IL-1. These findings suggested that both extracellular and intracellular collagen degradation played important roles in the stimulatory effect of IL-1 on collagen degradation by keratocytes.
- 1994-06-25