Effects and interactions of tumour necrosis factor alpha and bradykinin on interleukin-1 production in gingival fibroblasts

J Periodontal Res. 1995 May;30(3):186-91. doi: 10.1111/j.1600-0765.1995.tb01272.x.


Effects of and interactions between tumour necrosis factor alpha (TNF alpha) and bradykinin (BK) on production of interleukin-1 (IL-1 alpha, IL-1 beta) in human gingival fibroblasts were studied. The cytokine TNF alpha induced production of cell-associated IL-1 alpha and IL-1 beta in gingival fibroblasts, with IL-1 beta being most abundant. Addition of BK, in the presence of TNF alpha, for 1 h and 6 h, respectively, synergistically enhanced the TNF alpha induced IL-1 beta production, whereas BK alone did not induce IL-1 production. Similar to BK, two phorbol esters, phorbol 12,13 dibutyrate (PDBu) and phorbol 12-myristate-13-acetate (PMA) which are known to stimulate protein kinase C (PKC), synergistically enhanced the TNF alpha induced IL-1 beta production in the gingival fibroblasts. On the contrary, a phorbol ester which does not activate protein kinase C, 13-phorbolacetate (13-PA), did not potentiate the TNF alpha induced IL-1 beta production. Similar to BK, the phorbol esters (PMA, PDBu, 13-PA) alone did not induce IL-1 beta production in the gingival fibroblasts. The results indicate that TNF alpha induces production of cell-associated IL-1 in gingival fibroblasts, which can be upregulated by a PKC dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bradykinin / pharmacology*
  • Cells, Cultured
  • Child
  • Drug Synergism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Gingiva / cytology
  • Gingiva / metabolism*
  • Humans
  • Interleukin-1 / biosynthesis*
  • Phorbol Esters / pharmacology
  • Protein Kinase C / agonists
  • Protein Kinase C / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*
  • Up-Regulation


  • Interleukin-1
  • Phorbol Esters
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Protein Kinase C
  • Bradykinin