Protease-activated receptors (PARs) have a classical heptahelical structure within the plasma membrane and stimulate phosphoinositide turnover by coupling to G-protein. There are four known members of the receptor family of PARs: PAR-1, 3 and 4, which are activated by thrombin and gingipain, and PAR-2, which is activated by trypsin and mast cell tryptase. We previously demonstrated that IL-1α increased ESE-3 mRNA expression through MEK1/2 pathway in human oral epithelial cells (HO-1-N-1 cells). The present study was undertaken to investigate the interaction between interleukin-1α (IL-1α) and PAR-2 expressions in HO-1-N-1 cells. The cells were cultured to semi-confluence and treated with IL-1α or PAR-2 agonist for 6 - 24 hours. RNA was isolated from the cells, and IL-1α and PARs expressions were analyzed by RT-PCR. To measure the amount of IL-1α in cell culture supernatant, ELISA was performed according to the manufacturer's protocol using the Human IL-1α Quantikine ELISA Kit (R&D systems, MN, USA). HO-1-N-1 cells showed PAR-1 and PAR-2 mRNA expression. PAR-2 agonist increased IL-1α mRNA expression, and IL-1α increased PAR-2 mRNA expression in the dose dependent manner at 6 hours in HO-1-N-1 cells. PAR-2 agonist increased extracellular IL-1α level in HO-1-N-1 cells. These results suggest that IL-1α and PAR-2 may play an important role in inflammatory oral mucosal disease.