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- Title
Regulation of Proinflammatory Cytokines in Human Gestational Tissues by Peroxisome Proliferator-Activated Receptor-γ: Effect of 15-Deoxy-Δ<sup>12,14</sup>-PGJ<sub>2</sub> and Troglitazone.
- Authors
LAPPAS, MARTHA; PERMEZEL, MICHAEL; GEORGIOU, HARRY M.; RICE, GREGORY E.
- Abstract
Peroxisome proliferator-activated receptor (PPAR)-γ is a ligand-dependent nuclear receptor that is essential for murine placental development and trophoblast differentiation. In nonreproductive tissues, PPAR-γ regulates the formation of proinflammatory cytokines. Evidence suggests that many of the observed anti-inflammatory effects of PPAR-γ are in part caused by antagonizing the activities of the transcription factors, including nuclear factor-κB. The aim of this study was to elucidate whether natural [15-deoxy-Δ12,14-PGJ2 (15d-PGJ2)] and synthetic (troglitazone) PPAR-γ ligands regulate the secretion of IL-6, IL-8, and TNF-α from human intrauterine tissues. Human placenta, amnion, and choriodecidual tissues were incubated in the presence of 10 μg/ml lipopolysaccharide in the absence (control) or presence of 30 μm 15d-PGJ2 (n = 6 independent placenta) or troglitazone (n = 6 independent placentas). After a 6-h incubation, the incubation medium was collected and the release of IL-6, IL-8, and TNF-α was quantified by ELISA. Treatment of placental, amnion, and choriodecidual tissues with both 15d-PGJ2 and troglitazone significantly reduced the release of lipopolysaccharide-stimulated IL-6, IL-8, and TNF-α (t test, P < 0.05). Gel shift analyses demonstrated that 15d-PGJ2, but not troglitazone, suppressed nuclear factor-κB DNA-binding activity. The data presented in this study demonstrate that the formation of proinflammatory mediators can be modulated by currently available therapeutic agents and may therefore be of therapeutic potential in human labor.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2002, Vol 87, Issue 10, p4667
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.2002-020613