Cyclooxygenase-2-dependent prostaglandin E(2) upregulates interleukin (IL)-1alpha-induced IL-6 generation in mouse cementoblasts.
BACKGROUND
Prostaglandin E(2) (PGE(2)), which exerts its biologic actions via EP receptors (EP(1), EP(2), EP(3,) and EP(4)), is a bioactive metabolite of arachidonic acid that is produced by cyclooxygenase (COX)-1 and/or COX-2. In the present study, we investigated whether a mouse cementoblast cell line, OCCM-30 cells, that was stimulated with interleukin (IL)-1alpha produced COX-2-dependent PGE(2) and whether the produced PGE(2) affected IL-1alpha-induced IL-6 production.


METHODS
OCCM-30 cells were stimulated with vehicle or IL-1alpha in the presence or absence of indomethacin (a COX-1/COX-2 inhibitor), NS-398 (a specific COX-2 inhibitor), PGE(2), and EP receptor agonists. PGE(2) and IL-6 levels were assayed by enzyme linked immunosorbent assay.


RESULTS
IL-1alpha induced PGE(2) production in a time-dependent fashion. Indomethacin and NS-398 completely inhibited IL-1alpha-induced PGE(2) production. 17-phenyl-omega-trinor PGE(2) (an EP(1) agonist) and an EP(4) agonist mimicked PGE(2) enhancement of IL-1alpha-induced IL-6 production in OCCM-30 cells.


CONCLUSIONS
From these data, we suggest that IL-1alpha induced PGE(2) production in a COX-2-dependent manner in OCCM-30 cells and that the COX-2-derived PGE(2) upregulates IL-1alpha-elicited IL-6 production via EP(1) and/or EP(4) receptors. PGE(2) and IL-6 produced by cementoblasts may be involved in the pathogenesis of periodontal disease.
Noguchi
Kazuyuki
K
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. kazuyuki-noguchi.peri@tmd.ac.jp
Miyauchi
Mutsumi
M
Oka
Hiroko
H
Komaki
Motohiro
M
Somerman
Martha J
MJ
Takata
Takashi
T
D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003739:Dental Cementum / Q000166:cytology / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D053582:Interleukin-1alpha / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D053582:Interleukin-1alpha; D015850:Interleukin-6; D018078:Receptors, Prostaglandin E; D011994:Recombinant Proteins; D051546:Cyclooxygenase 2; D015232:Dinoprostone