Cyclooxygenase-2-derived prostaglandin E2 is involved in vascular endothelial growth factor production in interleukin-1alpha-stimulated human periodontal ligament cells

• Published in: Journal of periodontal research Vol. 44; no. 3; p. 395
• Main Authors: Bando, Y, Noguchi, K, Kobayashi, H, Yoshida, N, Ishikawa, I, Izumi, Y
• Format: Journal Article
• Language: English
• Published: United States 01.06.2009
• Subjects: Cells, Cultured; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Dinoprostone - metabolism; Humans; Indomethacin - pharmacology; Interleukin-1alpha - pharmacology; Interleukin-1alpha - physiology; Periodontal Ligament - cytology; Periodontal Ligament - drug effects; Periodontal Ligament - metabolism; Receptors, Prostaglandin E - agonists; Receptors, Prostaglandin E - metabolism; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Up-Regulation; Vascular Endothelial Growth Factor A - biosynthesis
• ISSN: 1600-0765; 1600-0765
• DOI: 10.1111/j.1600-0765.2008.01118.x

Prostaglandin E(2), which exerts its actions via EP receptors (EP1, EP2, EP3 and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase-1 and/or cyclooxygenase-2. Interleukin-1alpha induces prostaglandin E(2) production via cyclooxygenase-2 in human periodontal ligament cells. Vascular endothelial growth factor is a key regulator of physiologic as well as pathologic angiogenesis and has been indicated to be involved in the pathology of periodontal diseases. In the present study, we investigated whether interleukin-1alpha induced vascular endothelial growth factor production in human periodontal ligament cells and whether cyclooxygenase-2-derived prostaglandin E(2) regulated interleukin-1alpha-induced vascular endothelial growth factor production. Human periodontal ligament cells were obtained from extracted teeth of periodontally healthy subjects. After pre-incubation with a nonselective cyclooxygenase-1/2 inhibitor, indomethacin or a selective cyclooxygenase-2 inhibitor (NS-398), periodontal ligament cells were treated with or without interleukin-1alpha, prostaglandin E(2), various EP receptor agonists and dibutyryl cAMP (a cAMP analogue). The levels of vascular endothelial growth factor and prostaglandin E(2) in the culture supernatant were measured by enzyme-linked immunosorbent assay. The vascular endothelial growth factor mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction. Interleukin-1alpha induced vascular endothelial growth factor production in a dose-dependent and time-dependent manner. The interleukin-1alpha-induced vascular endothelial growth factor mRNA and protein expression was inhibited to the same extent by indomethacin and NS-398. Indomethacin and NS-398 completely inhibited interleukin-1alpha-induced prostaglandin E(2) production. Exogenous prostaglandin E(2), butaprost (an EP2 receptor agonist) and dibutyryl cAMP abolished the inhibitory effect of indomethacin on interleukin-1alpha-induced vascular endothelial growth factor production. We suggest that interleukin-1alpha induced vascular endothelial growth factor production via cyclooxygenase-2-derived prostaglandin E(2) in human periodontal ligament cells. The interleukin-1alpha/prostaglandin E(2) pathway might regulate vascular endothelial growth factor production in periodontal lesions.