Biological Roles of Liver X Receptors in Immune Cells

Pascual-García, Mónica; Valledor, Annabel F.

doi:10.1007/s00005-012-0179-9

Cited by 44 publications

(37 citation statements)

References 121 publications

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“…This effect seems to be quite surprising, as many studies report that LXR is mainly a negative regulator of inflammation by downregulating the expression of selective inflammatory genes (e.g., il1b, il6, inos, cox2, mmp9, mcp1, mcp3) through a process that involves DNA interaction, known as transrepression. 17,18 Here we show that LXRb is localized in the cytoplasm and has a non-genomic effect on the plasma membrane pore pannexin 1 (by direct interaction and activation) within the first minutes of agonist treatment, ruling out any transcriptional activity of LXR in our model. Some non-genomic effects of LXRb were previously described.…”

Section: Discussionmentioning

confidence: 60%

Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells

et al. 2014

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Liver X receptors (LXRs) have been proposed to have some anticancer properties, through molecular mechanisms that remain elusive. Here we report for the first time that LXR ligands induce caspase-1-dependent cell death of colon cancer cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3 (NLRP3) inflammasome and ATP-mediated P2 Â 7 receptor activation. Surprisingly, LXRb is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have an antitumoral effect in a mouse colon cancer model, dependent on the presence of LXRb, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXRb, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis.

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Section: Discussionmentioning

confidence: 60%

Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells

et al. 2014

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“…Two LXR isoforms have been defined, namely LXRa and LXRb, both activated by oxysterols and specific intermediates in the cholesterol biosynthetic pathway (revised in ref. [19]). LXRa is expressed in tissues with a high metabolic activity, including liver, adipose, and macrophages, whereas LXRb is ubiquitously expressed [19].…”

Section: Regulation Of Expressionmentioning

confidence: 99%

AIM/CD5L: a key protein in the control of immune homeostasis and inflammatory disease

Sanjurjo

Aran

Roher

et al. 2015

Journal of Leukocyte Biology

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111

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CD5L, a soluble protein belonging to the SRCR superfamily, is expressed mostly by macrophages in lymphoid and inflamed tissues. The expression of this protein is transcriptionally controlled by LXRs, members of the nuclear receptor family that play major roles in lipid homeostasis. Research undertaken over the last decade has uncovered critical roles of CD5L as a PRR of bacterial and fungal components and in the control of key mechanisms in inflammatory responses, with involvement in processes, such as infection, atherosclerosis, and cancer. In this review, we summarize the current knowledge of CD5L, its roles at the intersection between lipid homeostasis and immune response, and its potential use as a diagnostic biomarker in a variety of diseases, such as TB and liver cirrhosis.

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“…In addition, LXRs have been more recently associated with the modulation of the inflammatory response and innate immunity . LXRs negatively regulate the transcription of proinflammatory genes by antagonizing the actions of transcription factors such as nuclear factor‐κB (NF‐κB) .…”

Section: Introductionmentioning

confidence: 99%

Platelet‐activating factor downregulates the expression of liver X receptor‐α and its target genes in human neutrophils

et al. 2014

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Liver X receptors (LXRs) are ligand-activated members of the nuclear receptor superfamily that regulate the expression of genes involved in lipid metabolism and inflammation, although their role in inflammation and immunity is less well known. It has been reported that oxysterols/LXRs may act as anti-inflammatory molecules, although opposite actions have also been reported. In this study, we investigated the effect of platelet-activating factor (PAF), a proinflammatory molecule, on LXRa signalling in human neutrophils. We found that PAF exerted an inhibitory effect on mRNA expression of TO901317-induced LXRa, ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and sterol response element binding protein 1c. This negative action was mediated by the PAF receptor, and was dependent on the release of reactive oxygen species elicited by PAF, as it was enhanced by pro-oxidant treatment and reversed by antioxidants. Current data also support the idea that PAF induces phosphorylation of the LXRa molecule in an extracellular signal-regulated kinase 1/2-mediated fashion. These results suggest that a possible mechanism by which PAF exerts its proinflammatory effect is through the downregulation of LXRa and its related genes, which supports the notion that LXRa ligands exert a modulatory role in the neutrophil-mediated inflammatory response.

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Biological Roles of Liver X Receptors in Immune Cells

Cited by 44 publications

References 121 publications

Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells

Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells

AIM/CD5L: a key protein in the control of immune homeostasis and inflammatory disease

Platelet‐activating factor downregulates the expression of liver X receptor‐α and its target genes in human neutrophils

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