The symbiotic effects of P. gingivalis, T. denticola, and T. forsythia, which coaggregate and exist concomitantly in subgingival biofilms, may be associated with the local development of periodontitis.

We recently demonstrated that endothelin-1 (ET-1) was strongly expressed in inflamed gingival tissues, but the biological role of ET-1 in gingival tissue remains unknown. This study focused on the relationship between ET-1 and interleukin-1beta (IL-1beta), an important cytokine during the periodontal inflammatory process. We determined the protein levels of ET-1 and IL-1beta in gingival tissues from patients and examined whether ET-1 could regulate the expression of the IL-1beta gene and protein in oral epithelial cells and fibroblasts in vitro. There was a significant correlation between the levels of ET-1 and IL-1beta in 26 gingival tissues, as determined by ELISA. Following the confirmation of two specific ET-1 receptors (ETA and ETB receptors) on the cultured cells, the effects of ET-1 stimulation on IL-1beta mRNA and protein expression were evaluated by RT-PCR and ELISA, respectively. The IL-1beta mRNA and protein levels were enhanced by ET-1 stimulation in a dose-dependent manner, and the enhancement of IL-1beta was inhibited by ETA or ETB receptor antagonists. These findings indicate that ET-1 is involved in the regulation of IL-1beta expression in gingival tissues and suggest that ET-1 signaling to the cells may be a therapeutic target for treating IL-1beta-dependent inflammatory responses.

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