Differential regulation of interleukin-6 and inducible cyclooxygenase gene expression by cytokines through prostaglandin-dependent and -independent mechanisms in human dental pulp fibroblasts

J Endod. 2002 Mar;28(3):197-201. doi: 10.1097/00004770-200203000-00013.

Abstract

Increased levels of interleukin-1 (IL)-1, tumor necrosis factor-alpha (TNF-alpha), 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-1alpha or TNF-alpha 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-1alpha or TNF-alpha resulted in elevated levels of IL-6 (approximately 3.4 to approximately 10.4-fold) and COX-2 (approximately 5 to approximately 6.2-fold) mRNA. Simultaneous addition of IL-1alpha and PGE2 or TNF-alpha 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 approximately 1.7 to approximately 3.4-fold. This action could be reversed by exogenous PGE2. In contrast, PGE2 or indomethacin failed to modify the stimulatory effect of IL-1alpha or TNF-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Blotting, Northern
  • Cells, Cultured
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytokines / pharmacology*
  • Dental Pulp / cytology
  • Dental Pulp / metabolism*
  • Dinoprostone / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Indomethacin / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-6 / biosynthesis*
  • Isoenzymes / biosynthesis*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Pulpitis / metabolism*
  • RNA, Messenger / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Indomethacin