DUAL REGULATORY EFFECTS OF INTERFERON-ALPHA, INTERFERON-BETA, AND INTERFERON-GAMMA ON INTERLEUKIN-8 GENE-EXPRESSION BY HUMAN GINGIVAL FIBROBLASTS IN CULTURE UPON STIMULATION WITH LIPOPOLYSACCHARIDE FROM PREVOTELLA-INTERMEDIA, INTERLEUKIN-1-ALPHA, OR TUMOR-NECROSIS-FACTOR-ALPHA

In a previous study, we demonstrated that the amount of interleukin (I L)-8 mRNA expressed by human gingival fibroblasts stimulated with lipo polysaccharide (LPS) from Prevotella intermedia ATCC 25611 is increase d by pre-treatment with beta or gamma interferon (IFN-beta or -gamma). Ln the present study, we identified the regulatory effects of these I FNs on IL-8 mRNA expression and IL-8 production by human gingival fibr oblasts. Priming with IFN-alpha (alpha), -beta, or -gamma upregulated the IL-8 mRNA expression in response to P. intermedia LPS, whereas co- stimulation with these IFNs reduced the amount of mRNA expressed by th e cells. The regulation of IL-8 mRNA expression induced by recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) or rHuIL-1 alpha was similar to that induced by LPS. The IL-8 mRNA expression in response to P, intermedia LPS was enhanced by IFN-gamma independently of ne nov o protein synthesis, and was regulated, at least in part, at the trans criptional level. The IL-8 mRNA accumulation in response to P, interme dia LPS was inhibited by tosylphenyl-alanyl chloromethyl ketone, an in hibitor of NF-kappa B activation, although the NF-kappa B activation i tself was not altered by IFN-gamma. These findings suggest that IFNs m ight be capable of both enhancing end inhibiting inflammatory response s in periodontal tissues through the dual regulation of IL-8 productio n by gingival fibroblasts in response to bacterial components and cyto kines.