title: Prostaglandin E2 receptors EP1 and EP4 are up-regulated in rabbit chondrocytes by IL-1beta, but not by TNFalpha.
abstract: Prostaglandin E2 (PGE2) exerts its actions through the binding of the high affinity EP receptors. We wanted to evaluate the regulation of EP1 and EP4, and the expression of cyclooxygenase (COX)-2, main enzyme responsible for PGE2 synthesis in inflammatory situations, in healthy rabbit chondrocytes stimulated with inflammatory mediators locally increased during osteoarthritis. Articular chondrocytes obtained from healthy rabbits were stimulated with interleukin (IL)-1beta (0.1-100 u/ml) or tumour necrosis factor (TNF)alpha (100 ng/ml). Where indicated, cells were preincubated with non-steroidal antiinflammatory drugs (NSAIDs) (10(-6) M) to inhibit PGE2 synthesis. IL-1beta induced a dose and time-dependent increase in EP1, EP4 and COX-2 expression. However, TNFalpha presence did not induce a significant modification in EP1, EP4 or COX-2 gene expression at any time of study. NSAID presence significantly inhibited PGE2 release but did not modify the EP receptors or COX-2 expression induced by IL-1beta. Our results indicate that EP1 and EP4 receptors, and COX-2 are up-regulated in IL-1beta-stimulated chondrocytes, while no significant modifications are observed in TNFalpha-stimulated cells. NSAIDs were unable to modify the expression of these mediators induced by IL-1beta. Therefore, the increase in PGE2 synthesis, induced by IL-1beta, does not seem to mediate the increase in EP receptor expression, in rabbit chondrocytes.
authors.affiliation: Joint and Bone Research Unit, Fundación Jiménez Díaz, Universidad Autónoma, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Alvarez-Soria
authors.forename: Raquel
authors.initials: R
authors.lastname: Largo
authors.forename: Olga
authors.initials: O
authors.lastname: Sanchez-Pernaute
authors.forename: Emilio
authors.initials: E
authors.lastname: Calvo
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000502:physiology*; D007719:Knee Joint / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2