Prostaglandin E2 potentiates interleukin-1 beta induced interleukin-6 production by human gingival fibroblasts.
Increased levels of cytokines and prostanoids have been detected in inflamed gingival tissue and may play an important role in periodontal pathogenesis. Recent studies suggest that monocytic products, such as interleukin (IL)-1 beta, could stimulate IL-6 production by human gingival fibroblasts (HGF). In this context, the production of local cytokines and inflammatory mediators could regulate the secretory capacity of resident gingival fibroblasts. Therefore, the purpose of this study was to determine if PGE2 induced by IL-1 beta could potentiate the IL-6 response by HGF. Utilizing an ELISA, it was determined that maximal IL-6 occurred when HGF were stimulated with 0.10-10 nM IL-1 beta. These concentrations of IL-1 beta also induced a small, but significant increase in PGE2 production by HGF. Interestingly, the combination of IL gamma beta and PGE2 induced a synergistic rise in IL-6 production by HGF. Moreover, inclusion of indomethacin caused a 20% reduction in IL-6 production and totally eliminated PGE2 production. These findings provide additional rationale for the clinical use of NSAIDs in the management of periodontal disease due to their ability to attenuate production of both PGE2, and IL-6. These results suggest the endogenous PGE2 induced by IL-1 beta plays an important regulatory role in IL 6 production by HGF. Moreover, they support the concept that elevated PGE2induced during inflammation can regulate HGF secretory function.
Czuszak
C A
CA
Fort Leonard Wood Army Medical Center, Missouri, USA.
Sutherland
D E
DE
Billman
M A
MA
Stein
S H
SH
D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology* / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis*; D015854:Up-Regulation; D000093242:Interleukin-6 Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007213:Indomethacin; D007375:Interleukin-1; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors