EFFECTS AND INTERACTIONS OF TUMOR-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 T NF alpha induced production of cell-associated IL-1 alpha and IL-1 bet a in gingival fibroblasts, with IL-1 beta being most abundant. Additio n 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, w hereas BK alone did not induce IL-1 production. Similar to BK, two pho rbol 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 pot entiate 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 prod uction in the gingival fibroblasts. The results indicate that TNF alph a induces production of cell-associated IL-1 in gingival fibroblasts, which can be upregulated by a PKC dependent pathway.