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

• Published in: Journal of periodontal research Vol. 44; no. 3; pp. 395 - 401
• Main Authors: Bando, Y., Noguchi, K., Kobayashi, H., Yoshida, N., Ishikawa, I., Izumi, Y.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2009; Blackwell
• Subjects: Biological and medical sciences; interleukin-1; Medical sciences; Otorhinolaryngology. Stomatology; periodontal ligament cells; prostaglandin E2; vascular endothelial growth factor; Human; interleukin-1; Enzyme; Stomatology; Cyclooxygenase 2; Prostaglandin E2; Periodontal ligament; Vascular endothelium growth factor; vascular endothelial growth factor; Interleukin 1; periodontal ligament cells; Oxidoreductases; Cell
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/j.1600-0765.2008.01118.x

Background and Objective:  Prostaglandin E2, 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‐1α induces prostaglandin E2 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‐1α induced vascular endothelial growth factor production in human periodontal ligament cells and whether cyclooxygenase‐2‐derived prostaglandin E2 regulated interleukin‐1α‐induced vascular endothelial growth factor production. Material and Methods:  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‐1α, prostaglandin E2, various EP receptor agonists and dibutyryl cAMP (a cAMP analogue). The levels of vascular endothelial growth factor and prostaglandin E2 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. Results:  Interleukin‐1α induced vascular endothelial growth factor production in a dose‐dependent and time‐dependent manner. The interleukin‐1α‐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‐1α‐induced prostaglandin E2 production. Exogenous prostaglandin E2, butaprost (an EP2 receptor agonist) and dibutyryl cAMP abolished the inhibitory effect of indomethacin on interleukin‐1α‐induced vascular endothelial growth factor production. Conclusion:  We suggest that interleukin‐1α induced vascular endothelial growth factor production via cyclooxygenase‐2‐derived prostaglandin E2 in human periodontal ligament cells. The interleukin‐1α/prostaglandin E2 pathway might regulate vascular endothelial growth factor production in periodontal lesions.