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Treponema denticola suppresses the expression of IL-8 by gingival epithelial cells

Treponema denticola suppresses the expression of IL-8 by gingival epithelial cells

Abstracts of the General Meeting of the American Society for Microbiology 103: B-139

Homeostasis of the epithelial barrier in the mouth may depend on low-level inflammation that serves to keep the plaque bacteria in check. The potent neutrophil chemoattractant IL-8 is thought to form a gradient in healthy mouths, with the most IL-8 produced closest to the bacterial biofilm. In periodontal disease, this gradient is disrupted, preventing neutrophil chemotaxis to sites of bacterial overgrowth. Little is known about the ability of T. denticola to induce or suppress expression of inflammatory mediators by epithelial cells. Others have shown that dentilisin, the major outer membrane protease of T. denticola, degrades IL-8 in vitro. We now provide evidence that T. denticola also fails to induce IL-8 protein expression from primary gingival epithelial cells (GEC), and significantly reduces the amount of IL-8 induced by other stimuli, including LPS (50% reduction), Fusobacterium nucleatum cell walls (70% reduction), and PMA (30% reduction). This suppression of IL-8 secretion is not explained by IL-8 degradation, as a protease mutant that does not degrade IL-8 also suppresses IL-8 production by these stimuli. These agents induce IL-8 transcription via different pathways, suggesting that the inhibition of IL-8 expression must be downstream of a point common to all pathways. IL-8 expression can be regulated transcriptionally or posttranscriptionally. Our studies show that T. denticola is a weak inducer of IL-8 mRNA in GEC, and has minimal effects on IL-8 mRNA transcription induced by other stimuli. This suggests that T. denticola may exert its effects on IL-8 expression via posttranscriptional mechanisms. Not only can T. denticola degrade IL-8 present in the periodontal lesion, but this organism also suppresses further production of IL-8 protein by GEC. The 'chemokine paralysis' induced by T. denticola is similar to that exhibited by Porphyromonas gingivalis, another periodontal pathogen, and may contribute to the pathogenesis of periodontitis.

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Accession: 035985748

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