| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
We investigated the roles of prostaglandin E_2 (PGE_2) receptors, which are divided into EP1, EP2, EP3, EP4, in human gingival fibroblasts (HGF) and periodontal ligament (PDL) cells. HGF and PDL cells were stimulated with IL-1β and IL-1α, respectively, and produced IL-6 and PGE_2. Inhibition of endogenous PGE_2 by indomthacin, a cyclooxygenase inhibitor, enhanced IL-1-induced IL-6 production, although it completely inhibited IL-1-induced PGE_2 production. Exogenous PGE_2 suppressed IL-1-induced IL-6 production in both types of cells. 11-deoxy-PGE_1, a selective EP2/EP3/EP4 agonist, and butaprost, a selective EP2 agonist, inhibited IL-1-induced IL-6 production, although butaprost was less potent than 11-deoxy-PGE_1. ONO-AP-324, an EP3 agonist, could not affect IL-1-induced IL-6 production. 17-phenyl-ω-trinor PGE_2 enhanced IL-1-induced IL-6 production in HGF. Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression of EP2 and EP4 in PDL cells. Dibutyryl cAMP, a cAMP analog, and forskolin, an activator of adenylate cyclases, reduced IL-6 production by IL-1-stimulated cells
In conclusion, we suggest that PGE_2 downregulates IL-1-induced IL-6production via EP2/EP4 receptors by cAMP-dependent pathways in both HGF and PDL cells. EP2 and/or EP4 receptors may play critical roles in controlling inflammatory periodontal conditions.
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