title: IL-1beta stimulates the expression of prostaglandin receptor EP4 in human chondrocytes by increasing production of prostaglandin E2.
abstract: Prostaglandin (PG) E(2), which exerts its actions via the PG receptors EP1-4, is produced from arachidonic acid by cyclooxygenase (COX)-1 and COX-2. The aim of this study was to investigate the mechanisms by which interleukin (IL)-1beta induces the expression of PG receptors in cultured human chondrocytes and to explore the role of PGE(2) in this process. The cells were cultured with 0, 10, or 100 U/mL IL-1beta with or without 1 muM celecoxib, a specific inhibitor of COX-2, for up to 28 days. Expression of the genes encoding COX-1, COX-2, and EP1-4 was quantified using real-time PCR, and expression of the corresponding proteins was examined using immunohistochemical staining. PGE(2) production was determined using ELISA. IL-1beta treatment caused a marked dose- and time-dependent increase in the levels of PGE(2), COX-2, and EP4 as compared with the untreated control. It did not affect the expression of COX-1, and it decreased the expression of EP1 and EP2. EP3 expression was not detected in either the absence or the presence of IL-1beta. When celecoxib was also present, IL-1beta failed to stimulate PGE(2) production and EP4 expression, but its stimulatory effect on COX-2 expression and its inhibitory effect on EP1 and EP2 expression were unchanged. IL-1beta increases the production of PGE(2), COX-2, and the PG receptor EP4 in cultured human chondrocytes. The increase in EP4 expression appears to be a result of the increased PGE(2) production.
authors.affiliation: Nihon University Graduate School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Aki
authors.initials: A
authors.lastname: Namba
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Honda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Aida
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumura
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimizu
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanabe
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
mesh_terms: D000068579:Celecoxib; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000096:biosynthesis*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; C545650:PTGER4 protein, human; D011720:Pyrazoles; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone