Effects and interactions of tumour necrosis factor alpha and bradykinin on interleukin-1 production in gingival fibroblasts.
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.
D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000819:agonists / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D015854:Up-Regulation
D007375:Interleukin-1; D010703:Phorbol Esters; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D001920:Bradykinin