PURPOSE: Both activated keratocytes and infiltrated polymorphonuclear leukocytes (PMNs) contribute to corneal ulceration by degrading stromal collagen. The regulation of such collagen degradation by inflammatory cytokines was investigated with rabbit keratocytes and PMNs cultured in three-dimensional collagen gels. METHODS: Rabbit keratocytes or PMNs were cultured for 24 h in three-dimensional gels of type I collagen in the presence of plasminogen and various concentrations of either interleukin (IL)-1alpha, IL-6, IL-8, or tumor necrosis factor-alpha (TNF-alpha). Degradation of collagen during culture was assessed by measurement of released hydroxyproline. RESULTS: IL-1alpha increased the amount of collagen degraded by keratocytes or PMNs in a dose-dependent manner, whereas IL-6 had no effect on collagen degradation by either cell type. IL-8 increased the extent of collagen degradation by PMNs but not that by keratocytes, and TNF-alpha promoted collagen degradation by keratocytes but not that by PMNs. CONCLUSION: Inflammatory cytokines regulate collagen degradation by rabbit keratocytes and PMNs in culture in a differential manner, and therefore may contribute to the roles of these cells in corneal ulceration.
PURPOSE: Both activated keratocytes and infiltrated polymorphonuclear leukocytes (PMNs) contribute to corneal ulceration by degrading stromal collagen. The regulation of such collagen degradation by inflammatory cytokines was investigated with rabbit keratocytes and PMNs cultured in three-dimensional collagen gels. METHODS:Rabbit keratocytes or PMNs were cultured for 24 h in three-dimensional gels of type I collagen in the presence of plasminogen and various concentrations of either interleukin (IL)-1alpha, IL-6, IL-8, or tumor necrosis factor-alpha (TNF-alpha). Degradation of collagen during culture was assessed by measurement of released hydroxyproline. RESULTS:IL-1alpha increased the amount of collagen degraded by keratocytes or PMNs in a dose-dependent manner, whereas IL-6 had no effect on collagen degradation by either cell type. IL-8 increased the extent of collagen degradation by PMNs but not that by keratocytes, and TNF-alpha promoted collagen degradation by keratocytes but not that by PMNs. CONCLUSION: Inflammatory cytokines regulate collagen degradation by rabbit keratocytes and PMNs in culture in a differential manner, and therefore may contribute to the roles of these cells in corneal ulceration.