Peroxisome Proliferator-Activated Receptor Isoform Expression Changes in Human Gestational Tissues with Labor at Term

Berry, Elicia B. E.; Eykholt, R.L.; Helliwell, Rachel J. A.; Gilmour, R. Stewart; Mitchell, Murray D.; Marvin, Keith W.

doi:10.1124/mol.64.6.1586

Cited by 35 publications

(36 citation statements)

References 25 publications

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“…In the present study, we found that the PPAR-␦ ligand GW501516 (1 M) was also active in inhibiting IL-1␤-induced PGE 2 production, suggesting that the high concentration effect of 15d-PGJ 2 in WISH cells may be mediated, at least in part, through the activation of PPAR-␦. We have recently published data that support this argument, showing that the PPAR-␥ antagonist GW9662 is only partially effective at inhibiting 15d-PGJ 2 -induced activation of PPRE-driven reporter in JEG3 cells, whereas it completely abolished the rosiglitazone effect (Berry et al, 2003). The inhibition of 15d-PGJ 2 effects observed with the PPAR dominant-negative construct further supports the conclusion that 15d-PGJ 2 mediates its anti-inflammatory activity through the activation of PPARs because the PPAR D/N construct inhibits the transcriptional activity of all three PPAR isoforms (Berger et al, 2000).…”

Section: Discussionsupporting

confidence: 48%

Nanomolar and Micromolar Effects of 15-Deoxy-Δ12,14-prostaglandin J2 on Amnion-Derived WISH Epithelial Cells: Differential Roles of Peroxisome Proliferator-Activated Receptors γ and δ and Nuclear Factor κB

Berry¹,

Keelan²,

Helliwell³

et al. 2005

Molecular Pharmacology

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15-Deoxy ⌬12,14 -prostaglandin J 2 (15d-PGJ 2 ), an activator of peroxisome proliferator-activated receptor (PPAR)-␥ and -␦, 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 (Ͻ3 h) effects of 15d-PGJ 2 with rosiglitazone (PPAR-␥ ligand) and 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy-acetic acid (GW501516) (PPAR-␦ ligand) on interleukin (IL)-1␤-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 (Ͻ0.1 M), 15d-PGJ 2 inhibited IL-1␤-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-␥ inhibitor [2-chloro-5-nitro-N-phenylbenzamide (GW9662)], by transfection with a dominant-negative PPAR construct, and was reproduced by the PPAR-␥ ligand rosiglitazone. At higher concentrations (1-10 M), 15d-PGJ 2 inhibited IL-1␤-stimulated PGE 2 and cytokine production and COX-2 expression, and this effect was not blocked by GW9662. Rosiglitazone at high concentrations (1-10 M) stimulated PGE 2 production in the absence or presence of the dominant-negative PPAR. The PPAR-␦ ligand GW501516 also inhibited IL-1␤-stimulated PGE 2 production but only at high concentrations (1 M). IL-1␤-induced nuclear factor-B (NF-B) DNA binding activity was significantly inhibited by 15d-PGJ 2 (10 M) and GW501516 (1 M) but increased with 10 M rosiglitazone. We conclude that 1) at low concentrations, 15d-PGJ 2 acts through a PPAR-␥ signaling pathway; b) at higher concentrations, its actions are mediated most likely through other pathways such as activation of PPAR-␦ and/or inhibition of NF-B; and 3) rosiglitazone exerts PPAR-independent effects at high concentrations (Ͼ1 M).Proinflammatory cytokines have been shown to play crucial roles in the maintenance of human pregnancy and the initiation of parturition (Romero et al., 1993;Mitchell et al., 1995). The presence of intrauterine infection has been shown to result in the local expression and secretion of proinflammatory cytokines such as interleukin (IL)-1␤, tumor necrosis factor-␣, IL-6, and IL-8 (Romero et al., 1993;Dudley et al., 1996;Keelan et al., 1999a), which act locally on intrauterine cells to induce the release of inflammatory mediators, extracellular matrix-remodeling enzymes (So et al., 1992;Draper et al., 1995), and prostaglandins (PGs) through altered expression of prostanoid biosynthetic enzymes including fatty acid cyclooxygenase-2 (COX-2) Hansen et al., 1999;Kniss, 1999;Rauk and Chiao, 2000).Although most studies to date have focused on the produc- Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org. doi:10.1124/mol.104.009449.ABBREVIATIONS: IL, ...

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Section: Discussionsupporting

confidence: 48%

Nanomolar and Micromolar Effects of 15-Deoxy-Δ12,14-prostaglandin J2 on Amnion-Derived WISH Epithelial Cells: Differential Roles of Peroxisome Proliferator-Activated Receptors γ and δ and Nuclear Factor κB

Berry¹,

Keelan²,

Helliwell³

et al. 2005

Molecular Pharmacology

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“…PPARγ is expressed in the choriodecidual tissues [77], including decidual macrophages [78], where it was suggested to participate in the process of labor [79]. Recently, we reported that PPARγ activation (via rosiglitazone) attenuates the pro-inflammatory response at the maternal-fetal interface induced by a microbial product [78] or activation of invariant natural killer T cells [55].…”

Section: Resultsmentioning

confidence: 99%

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated in choriodecidual leukocytes compared to maternal circulating leukocytes. The most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and PLTP. The biological processes enriched in choriodecidual leukocytes were cell migration and regulation of immune response, chemotaxis, and humoral immune responses. Our results show striking differences between the transcriptome of choriodecidual and maternal circulating leukocytes. Choriodecidual leukocytes are enriched in immune mediators implicated in the spontaneous process of labor at term.

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“…PPAR , PPAR / and PPAR are also expressed in gestational tissues (in the amnion, choriodecidua, and placenta) (Berry et al 2003). PPAR / is strongly expressed during decidualization, and regulates embryo implantation (Lim & Dey 2000.…”

Section: Ppars -Mediators Of Endocrine Disruptors Of Environmental Ormentioning

confidence: 99%

Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition

Froment¹,

Gizard²,

Defever³

et al. 2006

Journal of Endocrinology

182

132

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Peroxisome Proliferator-Activated Receptor Isoform Expression Changes in Human Gestational Tissues with Labor at Term

Abstract: Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation.

Cited by 35 publications

References 25 publications

Nanomolar and Micromolar Effects of 15-Deoxy-Δ12,14-prostaglandin J2 on Amnion-Derived WISH Epithelial Cells: Differential Roles of Peroxisome Proliferator-Activated Receptors γ and δ and Nuclear Factor κB

Nanomolar and Micromolar Effects of 15-Deoxy-Δ12,14-prostaglandin J2 on Amnion-Derived WISH Epithelial Cells: Differential Roles of Peroxisome Proliferator-Activated Receptors γ and δ and Nuclear Factor κB

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition

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