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[Decreased stimulation of glycosaminoglycan synthesis in cultured human skin fibroblasts within the scope of in vitro aging caused by interleukin 1].

Addition of human recombinant interleukin-1 (IL-1 alpha or IL-1 beta) to culture medium (supplemented MEM without or with 1%, 10%, or 20% fetal calf serum (FCS)) of human skin fibroblasts exerted a stimulating effect in a dose-dependent manner on glycosaminoglycan (GAG) synthesis, including hyaluronic acid synthesis, of young (Phase II) skin fibroblasts in concentrations of 4, 20, or 100 pg/ml. Stimulation was due to increase in total GAGs, namely extracellular (secreted into culture medium) and cell-bound (pericellular) GAGs. Stimulation with 100 or 200 pg/ml IL-1 beta led to a relative increase (total GAGs: 100%) in hyaluronic acid from 49% to 64 (-FCS) and from 79% to 92% (+10% FCS), respectively. The increase in total GAG synthesis was mainly due to increased synthesis of hyaluronic acid. Maximum stimulation, with and without FCS, was reached by 100 pg/ml IL-1 beta. Compared to young (Phase II) cells senescent (Phase III) cells showed significantly diminished stimulation of hyaluronic acid synthesis by IL-1 beta. Both, IL-1 alpha and IL-1 beta, showed no influence on DNA synthesis. These results suggest that both, IL-1 beta and IL-1 alpha, stimulate GAG and especially hyaluronic acid synthesis, but not DNA synthesis, in vitro. The diminished response of GAG and hyaluronic acid synthesis during ageing of these in vitro cultured fibroblasts gives support to the hypothesis that similar processes might occur during ageing in organisms.