In the present study, the effect of prostaglandin E2 (PGE2) on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) stimulated with lipopolysaccharides (LPS) was investigated. LPS were isolated from periodontopathic bacteria, Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) and Porphyromonas gingivalis (P. gingivalis), by the phenol-water method and Escherichia coli (E. coli) LPS was used as a control. PGE2 significantly inhibited A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-induced ICAM-1 expression. Next, of four PGE2 receptor subtypes (EP1, EP2, EP3 and EP4), we examined which subtype(s) was involved in inhibition of LPS-elicited ICAM-1 expression by PGE2. Eleven-deoxy-PGE1, a selective EP2/EP4 agonist, and butaprost, a selective EP2 agonist, attenuated A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression, although butaprost was less potent than PGE2 and 11-deoxy-PGE1. Sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, was inert to the LPS-elicited ICAM-1 expression. Furthermore, dibutyryl cAMP, a cAMP analogue, and forskolin, an adenylate cyclase activator, downregulated A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression in HGF. Our data suggest that PGE2 downregulates A. actinomycetemcomitans- and P. gingivalis-LPS-induced ICAM-1 expression in HGF, via EP2/EP4 receptors by cAMP-dependent signaling pathways. The cAMP-elevating agents such as EP2/EP4 receptor activators may serve to control inflammatory and immune responses in periodontal disease.