Coordination of inflammation and metabolism by PPAR and LXR nuclear receptors

Hong, Cynthia; Tontonoz, Peter

doi:10.1016/j.gde.2008.07.016

Cited by 206 publications

(158 citation statements)

References 51 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…In addition, nuclear receptors are also known to modulate inflammatory signaling (22) and cell cycle progression (23), pathways that are important for successful infection.…”

mentioning

confidence: 99%

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Hwang¹,

Purdy

Wu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

An shRNA-mediated screen of the 48 human nuclear receptor genes identified multiple candidates likely to influence the production of human cytomegalovirus in cultured human fibroblasts, including the estrogen-related receptor α (ERRα), an orphan nuclear receptor. The 50-kDa receptor and a 76-kDa variant were induced posttranscriptionally following infection. Genetic and pharmacological suppression of the receptor reduced viral RNA, protein, and DNA accumulation, as well as the yield of infectious progeny. In addition, RNAs encoding multiple metabolic enzymes, including enzymes sponsoring glycolysis (enolase 1, triosephosphate isomerase 1, and hexokinase 2), were reduced when the function of ERRα was inhibited in infected cells. Consistent with the effect on RNAs, a substantial number of metabolites, which are normally induced by infection, were either not increased or were increased to a reduced extent in the absence of normal ERRα activity. We conclude that ERRα is needed for the efficient production of cytomegalovirus progeny, and we propose that the nuclear receptor contributes importantly to the induction of a metabolic environment that supports optimal cytomegalovirus replication.herpesvirus | metabolism | nuclear receptor | mass spectrometry H uman cytomegalovirus (HCMV) belongs to the β-herpesvirus subfamily, and although most healthy individuals remain asymptomatic subsequent to infection, the pathogen is a major contributor to birth defects and to life-threatening disease in immunocompromised patients (1-3). As with all viruses, HCMV depends on the host cell to provide macromolecular building blocks for virion production, and throughout the course of its evolution, HCMV has adapted to manipulate numerous fundamental cellular processes, including RNA accumulation (4), translation (5), metabolism (6, 7), secretory pathways (8), and the cell cycle (9).The nuclear receptor gene family, of which there are 48 members in the human genome, encodes transcription factors (10). Some bind to specific hydrophobic ligands such as steroids, vitamin D, fatty acids, and lipids, providing a means to sense changes in the extracellular or intracellular environment; others are "orphans" with no known ligand, and are often constitutively active (11). As transcription factors that modulate broad gene regulatory networks, nuclear receptors control numerous physiological processes, including aspects of metabolism (cell autonomously and at the whole-organism level), development, and cellular differentiation, cancer, circadian rhythm, and immunity (11).The first indication that nuclear receptor signaling modulates HCMV replication surfaced after the identification of a retinoic acid response element within the major immediate-early promoter (MIEP) that caused a dose-dependent response to retinoic acid in reporter assays (12). Retinoic acid was further shown to enhance viral DNA replication and progeny production in human embryonal carcinoma cells and foreskin fibroblasts (13,14). The ligand also exacerbated symptoms of infection,...

show abstract

“…In addition, nuclear receptors are also known to modulate inflammatory signaling (22) and cell cycle progression (23), pathways that are important for successful infection.…”

mentioning

confidence: 99%

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Hwang¹,

Purdy

Wu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Activation of PBMC by different stimuli such as fatty acids will enable them to alter the expression and release of cytokines and thereby the atherosclerotic process. It is well known that fatty acids act as ligands for the nuclear receptors PPAR (14) or may modulate the activity of Toll-like receptors (15,16) ; both mechanisms involve the NK-kB pathway and can thereby modulate the expression of pro-inflammatory factors (17) . Moderate or no effects on circulating inflammatory markers have been observed after the intake of a single meal with different fat quality (18 -21) .…”

mentioning

confidence: 99%

Effect of the fat composition of a single high-fat meal on inflammatory markers in healthy young women

et al. 2011

View full text Add to dashboard Cite

The aim of the present study was to examine the effect of a single high-fat meal with different fat quality on circulating inflammatory markers and gene expression in peripheral blood mononuclear cells (PBMC) to elucidate the role of fat quality on postprandial inflammation. A postprandial study with fourteen healthy females consuming three test meals with different fat quality was performed. Test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analysed. The test meal consisted of three cakes enriched with coconut fat (43 % energy as saturated fat and 1 % energy as a-linolenic acid (ALA)), linseed oil (14 % energy as ALA and 30 % energy as saturated fat) and cod liver oil (5 % energy as EPA and DHA and 5 % energy as ALA in addition to 31 % energy as saturated fat). In addition, ex vivo PBMC experiments were performed in eight healthy subjects investigating the effects of EPA and ALA on release and gene expression of inflammatory markers. The IL-8 mRNA level was significantly increased after intake of the cod liver oil cake at 6 h compared with fasting level, which was significantly different from the effect observed after the intake of linseed cake. In contrast, no effect was seen on circulating level of IL-8. In addition, ALA and EPA were shown to elicit different effects on the release and mRNA expression levels of inflammatory markers in PBMC cultured ex vivo, with EPA having the most prominent proinflammatory potential.

show abstract

“…22 LXRs inhibit inflammatory gene expression through the mechanism of trans-repression which is an event that depends on the direct binding of LXR to retinoid X-receptor for occupying promoters of target genes. 7 For instance, LXR activation in activated microglia and astrocytes inhibits the production of proinflammatory factors as NF-κB. 22 Joseph et al…”

Section: Discussionmentioning

confidence: 99%

“…6 These receptors have the ability to inhibit inflammatory gene expression through the mechanism of 'trans-repression' of transcription factors such as NF-ĸB. 7 Activation of these transcription factors modulates the inflammatory response of glial cells. [8][9][10] BSB disruption is one of the vascular events that happen in secondary injury after initial contusion and other forms of SCI such as transection.…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling ofliver X receptor αandBcl-2-associated X proteinin experimental transection spinal cord-injured rats

Mohammadi

Ghaedi

Esmailie

et al. 2013

The Journal of Spinal Cord Medicine

View full text Add to dashboard Cite

Background: Study of molecular responses to central nervous system injury would be helpful for controlling the harmful pathways post-injury and triggering the useful pathways required for the treatment of injury. Objective: To investigate the expression level of liver X receptor α (LXRα) which has anti-inflammatory effects and pro-apoptotic Bcl-2-associated X protein (Bax) upon spinal cord injury (SCI). Design: To induce SCI, transection was carried out at T9 level of male Wister rats. Approximately 8 mm of rostral, caudal, and epicenter tissues of injured sites in treated rats were chosen for quantitative real-time polymerase chain reaction at the 6, 24, and 72 hours, and 7 and 10 days post-surgery. Results: Our results showed a complicated temporal and spatial pattern of alteration in LXRα and Bax mRNA expression levels after SCI. LXRα expression level followed a homologues pattern (additive and subtractive wave) with a difference in time at three areas of studied. Rostral, caudal, and epicenter expression patterns of Bax were dissimilar in these areas. Gradual increase in the expression of Bax without any decrease at the rostral area was observed, presumably indicating the active transcription process of this gene, regardless of its protein situation. Conclusion: A time lapse significant change in Bax expression level was observed only in the epicenter of injury, emphasizing that apoptotic responses are limited to this area. Furthermore, an increase in LXRα transcription level was observed first in rostral area and then extended to epicentral and caudal areas, implying that inflammation responses extended from rostral to caudal areas.

show abstract

Coordination of inflammation and metabolism by PPAR and LXR nuclear receptors

Cited by 206 publications

References 51 publications

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Effect of the fat composition of a single high-fat meal on inflammatory markers in healthy young women

Gene expression profiling ofliver X receptor αandBcl-2-associated X proteinin experimental transection spinal cord-injured rats

Contact Info

Product

Resources

About