Differential regulation of interleukin-6 and inducible cyclooxygenase gene expression by cytokines through prostaglandin-dependent and -independent mechanisms in human dental pulp fibroblasts
Journal
Journal of Endodontics
Journal Volume
28
Journal Issue
3
Pages
197-201
Date Issued
2002
Author(s)
Abstract
Increased levels of interleukin-1 (IL)-1, tumor necrosis factor-α (TNF-α), IL-6, and prostaglandin E2 (PGE2) have been detected in inflamed pulp tissue. To gain further insight into the molecular pathogenesis of pulpitis, we investigated the effects of IL-1α or TNF-α and PGE2, either alone or in combination on IL-6 and cyclooxygenase (COX)-2 messenger RNA (mRNA) production in cultured human dental pulp (HDP) fibroblasts. Exposure of HDP fibroblasts to IL-1α or TNF-α resulted in elevated levels of IL-6 (?3.4 to ?10.4-fold) and COX-2 (?5 to ?6.2-fold) mRNA. Simultaneous addition of IL-1α and PGE2 or TNF-α and PGE2 to the cultures significantly reduced the cytokine-induced IL-6 mRNA synthesis ranging from 45% to 65%. However, indomethacin enhanced the cytokine-stimulated IL-6 mRNA synthesis by ?1.7 to ?3.4-fold. This action could be reversed by exogenous PGE 2. In contrast, PGE2 or indomethacin failed to modify the stimulatory effect of IL-1α or TNF-α on COX-2 gene expression. Because excessive levels of IL-6 and prostaglandins have been connected with the pathogenesis of several inflammatory diseases, our results suggest the involvement of HDP fibroblasts in the development of pulpitis via producing IL-6 and COX-2. Furthermore, expression of IL-6 and COX-2 genes in this cell seems to be differentially regulated by cytokines through prostaglandin-dependent and -independent pathways. Copyright ? 2002 by The American Association of Endodontists.
SDGs
Other Subjects
cyclooxygenase 2; cyclooxygenase 2 inhibitor; cytokine; indometacin; interleukin 1; interleukin 6; isoenzyme; membrane protein; messenger RNA; nonsteroid antiinflammatory agent; prostaglandin E2; prostaglandin synthase; prostaglandin synthase inhibitor; PTGS2 protein, human; tumor necrosis factor alpha; article; biosynthesis; cell culture; cytology; drug effect; gene expression regulation; human; metabolism; Northern blotting; pulpitis; tooth pulp; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Northern; Cells, Cultured; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cytokines; Dental Pulp; Dinoprostone; Gene Expression Regulation; Humans; Indomethacin; Interleukin-1; Interleukin-6; Isoenzymes; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Pulpitis; RNA, Messenger; Tumor Necrosis Factor-alpha
Type
journal article