Abstract
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.