070 Reduction of IL-8 Secretion in Senescent Fibroblasts: Role in Chronic Wound Formation.

Abstract

Fibroblasts in chronic wounds, and in skin in which ulcers develop, have been reported to show characteristics of senescence, presumably induced by conditions predisposing to chronic wounds or the wound environment. In monolayer culture, secretion of IL-8 declines to zero as the cells approach senescence (at about generations 50–55 in the cells tested). In three-dimensional scaffold-based tissue culture, fibroblasts, at about 30–35 population doublings, upregulate the IL-8 gene by comparison with monolayer cultures and secrete large amounts of IL-8 (30–50 ng/106 cells/day). However, it is inferred that a decline in secretion, similar to that seen in monolayer also occurs in three-dimensional culture and in the senescent fibroblasts of chronic wounds. This will result in decreased influx and activation of neutrophils. The hypothesis is proposed that chronic wounds arise because fibroblasts, following injury to ulcer-prone skin, do not recruit and activate neutrophils sufficiently to prevent bacterial colonization. As the result of the persistent presence of live bacteria, inflammatory cells or keratinocytes in a wound site may be expected to trigger mechanisms to inhibit keratinocyte migration and reepithelialization, leading to chronic ulceration.