Prostaglandin E2 (PGE2) downregulates interleukin (IL)-1alpha-induced IL-6 production via EP2/EP4 subtypes of PGE2 receptors in human periodontal ligament cells.
OBJECTIVE
Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are divided into four subtypes, EP1, EP2, EP3 and EP4. In the present study, we examined whether PGE2 regulated interleukin (IL)-1alpha-induced IL-6 production in human periodontal ligament (PDL) cells and if so, which subtypes of PGE2 receptors were involved.


METHODS
PDL cells were stimulated with vehicle or IL-1alpha in the presence or absence of indomethacin (a cylooxygenase inhibitor), PGE2 or various EP agonists. IL-6 and PGE2 levels were measured by enzyme-linked immunosorbent assay. EP receptor mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Indomethacin significantly enhanced IL-1alpha-induced IL-6 production by PDL cells, although it completely inhibited IL-1alpha-induced PGE2 production. Exogenous PGE2 significantly suppressed IL-1alpha-induced IL-6 production. Butaprost, a selective EP2 agonist, and ONO-AE1-329, a selective EP4 agonist, significantly inhibited IL-1alpha-induced IL-6 production, although 17-phenyl-omega-trinor PGE2, an EP1 agonist, and ONO-AP-324, an EP3 agonist, did not affect it. RT-PCR analysis showed that EP2 and EP4 mRNA was expressed in PDL cells.


CONCLUSIONS
We suggest that PGE2 downregulates IL-1alpha-induced IL-6 production via EP2/EP4 receptors in human PDL cells.
Noguchi
K
K
Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. kazuyuki-noguchi.peri@tmd.ac.jp
Maeda
M
M
Ruwanpura
S M P M
SM
Ishikawa
I
I
D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000187:drug effects / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone; D007213:Indomethacin