The effect of interleukin-1 β on hyaluronic acid synthesized by adult human gingival fibroblasts in vitro

The effect of recombinant interleukin-1β (IL-lβ) on hyaluronic acid synthesis by human gingival fibroblasts was studied. IL-1bT caused a dose-dependent increase in the incorporation of (³lucosamine into hyaluronic acid. The ³⁵S/35H ratios of labeled macromolecules did not change regardless of the presence or absence of TL-lβ and indicates stimulation of hyaluronic acid synthesis. Inhibition of cell proliferation by hydroxyurea caused an increase in hyaluronic acid synthesis. The effect of IL-1β on hyaluronic acid synthesis in the presence of hydroxyurea was increased over untreated and IL-lβ-treated controls, but equivalent to the hydroxyurea-treated controls. Thus the effect of IL-1β on hyaluronic acid synthesis may be independent of cell proliferation. Furthermore, inhibition of prostaglandin E2 synthesis by indomethacin abolished the effect of IL-1β on hyaluronic acid synthesis. Inhibition of new protein synthesis by cycloheximide negated the effect of IL-β on hyaluronic acid synthesis. This may be related to inhibition of new hyaluronate synthetase synthesis, since IL-1β stimulated the level of hyaluronate synthetase activity. Sepharose CL-2B chromatography revealed that most of the newly synthesized hyaluronic acid was of large molecular size. The cells exposed to IL-1β retained more large molecular size hyaluronic acid in their cell layer environment than did the control cells. These responses by fibroblasts to IL-1β may be indicative of early tissue repair.