Dual Regulatory Effects of Interferon-α, -β, and -γ on Interleukin-8 Gene Expression by Human Gingival Fibroblasts in Culture upon Stimulation with Lipopolysaccharide from Prevotella intermedia, Interleukin-1α, or Tumor Necrosis Factor-α

Abstract

In a previous study, we demonstrated that the amount of interleukin (IL)-8 mRNA expressed by human gingival fibroblasts stimulated with lipopolysaccharide (LPS) from Prevotella intermedia ATCC 25611 is increased by pre-treatment with beta or gamma interferon (IFN-β or --y). In the present study, we identified the regulatory effects of these IFNs on IL-8 mRNA expression and IL-8 production by human gingival fibroblasts. Priming with IFN-alpha (a), -β, or --y 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 the cells. The regulation of IL-8 mRNA expression induced by recombinant human tumor necrosis factor-a (rHuTNF-a) or rHuIL-1α was similar to that induced by LPS. The IL-8 mRNA expression in response to P. intermedia LPS was enhanced by IFN-γ independently of de novo protein synthesis, and was regulated, at least in part, at the transcriptional level. The IL-8 mRNA accumulation in response to P. intermedia LPS was inhibited by tosylphenyl-alanyl chloromethyl-ketone, an inhibitor of NF-KB activation, although the NF-KB activation itself was not altered by IFN-γ. These findings suggest that IFNs might be capable of both enhancing and inhibiting inflammatory responses in periodontal tissues through the dual regulation of IL-8 production by gingival fibroblasts in response to bacterial components and cytokines.