Regulation of collagen expression by interleukin-1 beta is dependent on donor age.

Abstract

Cultured skin fibroblasts derived from old (> 60 years) donors differ in various morphological and functional aspects from cells obtained from young (< 20 years) donors. We were interested in whether fibroblasts obtained from old and young donors differ in their cellular response to interleukin-1 beta, a cytokine which has been shown to affect the synthesis of extracellular matrix proteins in human dermal fibroblasts. Therefore the expression of interstitial collagen (type I), minor collagen (type VI) and interstitial collagenase genes was investigated, using fibroblasts derived from either old or young donors. Fibroblasts were incubated in the absence or presence of interleukin-1 beta (5 units/ml, 50 units/ml, 500 units/ml) for 48 h. Total RNA was isolated and mRNA levels were determined by Northern and dot blot analysis. Comparing the synthetic response of fibroblasts obtained from young and old donors, we observed a marked increase of the inhibition of type I and type VI collagen expression and the stimulation of interstitial collagenase in the aged fibroblasts. These results suggest that physiological ageing in human fibroblasts is associated with an altered responsiveness to interleukin-1 beta.