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

Effects of and interactions between tumour necrosis factor α (TNFα) and bradykinin (BK) on production of interleukin-1 (IL-lα, IL-lβ) in human gingival fibroblasts were studied. The cytokine TNFα induced production of cell-associated IL-lα and IL-1β in gingival fibroblasts, with IL-lβ being most abundant. Addition of BK, in the presence of TNFα, for 1 h and 6 h, respectively, synergistically enhanced the TNFα induced IL-lβ production, whereas BK alone did not induce 1L-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 TNFα induced IL-lβ 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 TNFα induced IL-lβ production. Similar to BK, the phorbol esters (PMA, PDBu, 13-PA) alone did not induce IL-1β production in the gingival fibroblasts. The results indicate that TNFα induces production of cell-associated IL-1 in gingival fibroblasts, which can be upregulated by a PKC dependent pathway.