15-Deoxy-12,14-prostaglandin J2 inhibits interferon gamma induced MHC class II but not class I expression on ARPE cells through a PPAR gamma independent mechanism

Willermain, François; Dulku, Simon; Gonzalez, Nathalie Suarez; Bléro, Daniel; Driessens, Grégory; Graef, Chantal De; Caspers, Laure; Bruyns, Catherine

doi:10.1016/j.prostaglandins.2006.06.001

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…Unexpectedly, the natural PPARγ agonist PGJ2 exerted no effect on HIV replication, in contrast to previous studies on different cell types [66,114], suggesting that PGJ2 effects are cell-dependent. One potential explanation is related to the fact that PGJ2 exerts PPARγ-independent effects [115]. Another explanation may be that Th1Th17 selectively express transcripts for hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) (Table 1), an enzyme involved in PGs degradation [116].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies Peroxisome Proliferator-Activated Receptor Gammaas an intrinsic negative regulator of viral replication

et al. 2013

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BackgroundWe previously demonstrated that primary Th1Th17 cells are highly permissive to HIV-1, whereas Th1 cells are relatively resistant. Molecular mechanisms underlying these differences remain unknown.ResultsExposure to replication competent and single-round VSV-G pseudotyped HIV strains provide evidence that superior HIV replication in Th1Th17 vs. Th1 cells was regulated by mechanisms located at entry and post-entry levels. Genome-wide transcriptional profiling identified transcripts upregulated (n = 264) and downregulated (n = 235) in Th1Th17 vs. Th1 cells (p-value < 0.05; fold change cut-off 1.3). Gene Set Enrichment Analysis revealed pathways enriched in Th1Th17 (nuclear receptors, trafficking, p38/MAPK, NF-κB, p53/Ras, IL-23) vs. Th1 cells (proteasome, interferon α/β). Differentially expressed genes were classified into biological categories using Gene Ontology. Th1Th17 cells expressed typical Th17 markers (IL-17A/F, IL-22, CCL20, RORC, IL-26, IL-23R, CCR6) and transcripts functionally linked to regulating cell trafficking (CEACAM1, MCAM), activation (CD28, CD40LG, TNFSF13B, TNFSF25, PTPN13, MAP3K4, LTB, CTSH), transcription (PPARγ, RUNX1, ATF5, ARNTL), apoptosis (FASLG), and HIV infection (CXCR6, FURIN). Differential expression of CXCR6, PPARγ, ARNTL, PTPN13, MAP3K4, CTSH, SERPINB6, PTK2, and ISG20 was validated by RT-PCR, flow cytometry and/or confocal microscopy. The nuclear receptor PPARγ was preferentially expressed by Th1Th17 cells. PPARγ RNA interference significantly increased HIV replication at levels post-entry and prior HIV-DNA integration. Finally, the activation of PPARγ pathway via the agonist Rosiglitazone induced the nuclear translocation of PPARγ and a robust inhibition of viral replication.ConclusionsThus, transcriptional profiling in Th1Th17 vs. Th1 cells demonstrated that HIV permissiveness is associated with a superior state of cellular activation and limited antiviral properties and identified PPARγ as an intrinsic negative regulator of viral replication. Therefore, triggering PPARγ pathway via non-toxic agonists may contribute to limiting covert HIV replication and disease progression during antiretroviral treatment.

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Section: Discussionmentioning

confidence: 99%

Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies Peroxisome Proliferator-Activated Receptor Gammaas an intrinsic negative regulator of viral replication

et al. 2013

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“…4). Though reports directly linking PPARc dysfunction with human AMD pathology are limited, follow-up functional studies using ARPE19 and/or primary cells have speculated that it plays a role in AMD by targeting oxidative stress and inflammation [154, 165– 169] (though as discussed earlier, caution is necessary in interpreting these cell culture models, until the NR of interest has been shown to be definitely expressed in the aged human eye cells). Still, it is probable that in vivo targeting of PPARγ may have a therapeutic benefit given the role of macrophages in AMD and data from the atherosclerosis field demonstrating PPARs as negative regulators of macrophage activation.…”

Section: Nuclear Receptors As Regulators Of Amd Biologymentioning

confidence: 99%

Emerging roles for nuclear receptors in the pathogenesis of age-related macular degeneration

Malek

Lad

2014

Cell. Mol. Life Sci.

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Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly in the Western world. Over the last 30 years, our understanding of the pathogenesis of the disease has grown exponentially thanks to the results of countless epidemiology, genetic, histo-logical, and biochemical studies. This information, in turn, has led to the identification of multiple biologic pathways potentially involved in development and progression of AMD, including but not limited to inflammation, lipid and extracellular matrix dysregulation, and angiogenesis. Nuclear receptors are a superfamily of transcription factors that have been shown to regulate many of the pathogenic pathways linked with AMD and as such they are emerging as promising targets for therapeutic intervention. In this review, we will present the fundamental phenotypic features of AMD and discuss our current understanding of the pathobiological disease mechanisms. We will introduce the nuclear receptor superfamily and discuss the current literature on their effects on AMD-related pathophysiology.

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“…Since EPA has recently been shown to have similar effects on ER calcium discharge [111, 115], it seems likely that various other PUFAs activate the ER stress pathway. Nonetheless, PPAR γ activators often show very different side effects [42, 103, 116–120]. For example, among three PPAR γ agonists, ciglitazone, 9-HODE, and 13-HODE, only 9-HODE induced apoptosis in U937 cells [38], 15d-Δ 12,14 -PGJ 2 , but not various other PPAR γ ligands, reduced EGFR expression in squamous carcinoma cells [99], 15d-Δ 12,14 -PGJ 2 , but not troglitazone, inhibited the stimulated induction of MHC class II molecules in retinal pigmented epithelial cells [112], and DHA, but not EPA, stimulated the target gene, syndecan 1 to inhibit the proliferation and induce apoptosis in breast and prostate cancer cell lines [75, 76, 96].…”

Section: Targets Of Pparγ Relevant To Cancermentioning

confidence: 99%

“…For example, among three PPAR γ agonists, ciglitazone, 9-HODE, and 13-HODE, only 9-HODE induced apoptosis in U937 cells [38], 15d-Δ 12,14 -PGJ 2 , but not various other PPAR γ ligands, reduced EGFR expression in squamous carcinoma cells [99], 15d-Δ 12,14 -PGJ 2 , but not troglitazone, inhibited the stimulated induction of MHC class II molecules in retinal pigmented epithelial cells [112], and DHA, but not EPA, stimulated the target gene, syndecan 1 to inhibit the proliferation and induce apoptosis in breast and prostate cancer cell lines [75, 76, 96]. Numerous other examples of differential effects among PPAR γ agonists exist (e.g., [113–116]), but it is worth stressing that n-3 PUFAs inhibit the metabolism of n-6 PUFAs to products that promote the growth of cancer cells such as PGE 2 , 5-HETE, and leukotriene B 4 [33–35, 45, 113]. This inhibitory effect may make an important contribution to the anticancer effects of n-3 PUFAs.…”

Section: Targets Of Pparγ Relevant To Cancermentioning

confidence: 99%

Omega‐3 Fatty Acids and PPARγ in Cancer

2008

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Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γ and, due to the effects of PPARγ on cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal models. In vitro studies have shown that omega-3 PUFAs inhibit cell proliferation and induce apoptosis in cancer cells through various pathways but one of which involves PPARγ activation. The differential activation of PPARγ and PPARγ-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relating PUFAs to PPARγ and cancer and offers a new paradigm relating an n-3 PUFA through PPARγ to the expression of the cell surface proteoglycan, syndecan-1, and to the death of cancer cells.

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15-Deoxy-12,14-prostaglandin J2 inhibits interferon gamma induced MHC class II but not class I expression on ARPE cells through a PPAR gamma independent mechanism

Cited by 9 publications

References 20 publications

Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies Peroxisome Proliferator-Activated Receptor Gammaas an intrinsic negative regulator of viral replication

Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies Peroxisome Proliferator-Activated Receptor Gammaas an intrinsic negative regulator of viral replication

Emerging roles for nuclear receptors in the pathogenesis of age-related macular degeneration

Omega‐3 Fatty Acids and PPARγ in Cancer

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