دورية أكاديمية
Nanomolar and micromolar effects of 15-deoxy-delta 12,14-prostaglandin J2 on amnion-derived WISH epithelial cells: differential roles of peroxisome proliferator-activated receptors gamma and delta and nuclear factor kappa B.
| العنوان: | Nanomolar and micromolar effects of 15-deoxy-delta 12,14-prostaglandin J2 on amnion-derived WISH epithelial cells: differential roles of peroxisome proliferator-activated receptors gamma and delta and nuclear factor kappa B. |
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| المؤلفون: | Berry EB; Liggins Institute, University of Auckland, Faculty of Medical & Health Sciences, Auckland, New Zealand., Keelan JA, Helliwell RJ, Gilmour RS, Mitchell MD |
| المصدر: | Molecular pharmacology [Mol Pharmacol] 2005 Jul; Vol. 68 (1), pp. 169-78. Date of Electronic Publication: 2005 Apr 08. |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0035623 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0026-895X (Print) Linking ISSN: 0026895X NLM ISO Abbreviation: Mol Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Society for Pharmacology and Experimental Therapeutics |
| مواضيع طبية MeSH: | Amnion/*drug effects , Epithelial Cells/*drug effects , NF-kappa B/*physiology , PPAR delta/*physiology , PPAR gamma/*physiology , Prostaglandin D2/*administration & dosage , Prostaglandin D2/*analogs & derivatives, Amnion/cytology ; Amnion/physiology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Epithelial Cells/cytology ; Epithelial Cells/physiology ; Humans ; Nanotechnology/methods |
| مستخلص: | 15-Deoxy delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an activator of peroxisome proliferator-activated receptor (PPAR)-gamma and -delta, is a prostanoid metabolite with anti-inflammatory actions. In intrauterine tissues, proinflammatory cytokines and prostaglandins have been identified as playing key roles in the maintenance of pregnancy and the onset of labor. We investigated and compared the early (<3 h) effects of 15d-PGJ(2) with rosiglitazone (PPAR-gamma ligand) and 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy-acetic acid (GW501516) (PPAR-delta ligand) on interleukin (IL)-1beta-induced prostaglandin and cytokine production by amnion-derived WISH cells. We show that 15d-PGJ(2) exerts differential effects depending on concentration. At low concentrations (<0.1 microM), 15d-PGJ(2) inhibited IL-1beta-stimulated prostaglandin E(2) (PGE(2)) but not cytokine (IL-6/IL-8) production or cyclooxygenase-2 (COX-2) expression. This effect was attenuated by a PPAR-gamma inhibitor [2-chloro-5-nitro-N-phenyl-benzamide (GW9662)], by transfection with a dominant-negative PPAR construct, and was reproduced by the PPAR-gamma ligand rosiglitazone. At higher concentrations (1-10 microM), 15d-PGJ(2) inhibited IL-1beta-stimulated PGE(2) and cytokine production and COX-2 expression, and this effect was not blocked by GW9662. Rosiglitazone at high concentrations (1-10 microM) stimulated PGE(2) production in the absence or presence of the dominant-negative PPAR. The PPAR-delta ligand GW501516 also inhibited IL-1beta-stimulated PGE(2) production but only at high concentrations (1 microM). IL-1beta-induced nuclear factor-kappaB (NF-kappaB) DNA binding activity was significantly inhibited by 15d-PGJ(2) (10 microM) and GW501516 (1 microM) but increased with 10 microM rosiglitazone. We conclude that 1) at low concentrations, 15d-PGJ(2) acts through a PPAR-gamma signaling pathway; b) at higher concentrations, its actions are mediated most likely through other pathways such as activation of PPAR-delta and/or inhibition of NF-kappaB; and 3) rosiglitazone exerts PPAR-independent effects at high concentrations (>1 microM). |
| المشرفين على المادة: | 0 (15-deoxyprostaglandin J2) 0 (NF-kappa B) 0 (PPAR delta) 0 (PPAR gamma) RXY07S6CZ2 (Prostaglandin D2) |
| تواريخ الأحداث: | Date Created: 20050412 Date Completed: 20050801 Latest Revision: 20131121 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1124/mol.104.009449 |
| PMID: | 15821150 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0026-895X |
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| DOI: | 10.1124/mol.104.009449 |