The purpose of this study is to reveal the molecular mechanism of infection between periodontal pathogenic bacteria and host cells using cellular and molecular biological approaches, and to analyze the function of pathogenic proteases produced by periodontal pathogenic bacteria to clarify the pathogenesis of periodontal disease. In this study, we focused on gingipains, which are cysteine proteases, produced by Porphyromonas gingivalis (P. gingivalis), to elucidate the pathogenesis of periodontal disease infected with P. gingivalis. We examined the host cell response to the molecular mechanism of COX-2 expression by gingipains and showed that activation of two signaling pathways, ERK and IKK, and found that intracellular calcium is required for COX-2 expression and PGE2 production as the upstream factors.