Cyclooxygenase‐2–Dependent Prostaglandin E2 Upregulates Interleukin (IL)‐1α–Induced IL‐6 Generation in Mouse Cementoblasts

Abstract

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. 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. 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. 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.