Prostaglandin E₂ inhibits interleukin-6 release but not its transcription in human gingival fibroblasts stimulated with interleukin-1β or tumor necrosis factor-α

Inflammatory mediators produced by human gingival fibroblasts (HGF) have been implicated in the initiation and progression of periodontal disease. The purpose of this study was to examine whether prostaglandin E₂ (PGE₂), which is produced in abundance from HGF after stimulation with interleukin (IL)-1β or tumor necrosis factor-α (TNF-α), could regulate IL-6 production by HGF. HGF stimulated with either IL-1β or TNF-α showed a rapid and dose-dependent increase in IL-6 mRNA accumulation and IL-6 secretion, as demonstrated by reverse transcription-polymerase chain reaction analysis and bioassay. IL-6 secretion from either IL-1β- or TNF-α-stimulated HGF was enhanced by the inhibition of PGE₂ synthesis with indomethacin. Furthermore, the addition of PGE₂ inhibited IL-6 secretion from these cells. In contrast, indomethacin or PGE₂ did not affect the accumulation of IL-6 mRNA in IL-1β-stimulated HGF. These data indicate that IL-6 production by HGF is up-regulated by specific cytokines, IL-1β and TNF-α, and suggest that this production may be partially down-regulated by endogenous and exogenous PGE₂ at the post-transcriptional level.