Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-κBp50

Canavan, Mary; McCarthy, Ciara; Larbi, Nadia Ben; Dowling, Jennifer K.; Collins, Laura; O’Sullivan, Finbarr; Hurley, Gráinne; Murphy, C.; Quinlan, Aoife; Moloney, Gerard M.; Darby, Trevor; MacSharry, John; Kagechika, Hiroyuki; Moynagh, Paul N.; Melgar, Silvia; Loscher, Christine E.

doi:10.1177/1753425913501915

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…In the CNS, LXRs are widespread in growing or mature neurons and glial cells (Mandrekar-Colucci and Landreth, 2011). Recent studies showed that LXRα could disrupt NF-κB activation by a process called trans -repression and thus has an anti-inflammatory function (Zhang-Gandhi and Drew, 2007; Mandrekar-Colucci and Landreth, 2011; Cui et al, 2012; Canavan et al, 2013). Therefore, we investigated the role of miR-155-LXRα in regulating the heat stress-induced inflammatory response to elucidate the underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-155 Promotes Heat Stress-Induced Inflammation via Targeting Liver X Receptor α in Microglia

Gong

Zhang

et al. 2019

Front. Cell. Neurosci.

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Background: The neuroinflammatory responses of microglial cells play an important role in the process of brain dysfunction caused by heat stroke. MicroRNAs are reportedly involved in a complex signaling network and have been identified as neuroinflammatory regulators. In this study, we determined the biological roles of microRNA-155 in the inflammatory responses in heat-stressed microglia and explored the underlying mechanisms.Methods: MicroRNA-155 mimic and inhibitor were used to separately upregulate or downregulate microRNA-155 expression. The activation state of BV-2 microglial cells (BV-2 cells) was assessed via immunoreactions using the microglial marker CD11b and CD68. Levels of induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assays (ELISAs). The activation of nuclear factor kappa B (NF-κB) signaling proteins was evaluated by Western blotting for inhibitory kappa B alpha (IκBα) and NF-κB p65 phosphorylation and indirect immunofluorescence analysis using a p65 phosphorylation antibody. A luciferase reporter assay was used to verify liver X receptor α (LXRα) as a target gene of microRNA-155.Results: Heat stress significantly induced IL-1β, IL-6, and TNF-α release and increased the expression of CD11b and CD68. In addition, IκBα and NF-κB p65 phosphorylation were dramatically increased by heat stress, and microRNA-155 expression was also elevated. High expression of microRNA-155 in heat-stressed microglial cells was inversely correlated with LXRα expression. We then determined the role of microRNA-155 in the heat stress-induced inflammatory responses. The results revealed that by targeting LXRα, microRNA-155 enhanced NF-κB signaling activation and facilitated immune inflammation in heat stress-treated BV-2 cells.Conclusion: MicroRNA-155 promotes heat stress-induced inflammatory responses in microglia. The underlying mechanisms may include facilitating inflammatory factors expression by increasing NF-κB pathway activation via targeting LXRα.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-155 Promotes Heat Stress-Induced Inflammation via Targeting Liver X Receptor α in Microglia

Gong

Zhang

et al. 2019

Front. Cell. Neurosci.

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“…These data suggest that acute LPS treatment induces important early transcription factors and coordinately down-regulates nuclear receptors, resulting in altered expression of a large number of downstream genes (Fang et al, 2004). Canavan et al (2013) first demonstrated that activation of murine-derived dendritic cells with a specific agonist to LXR enhanced expression of LXR following activation with LPS. Wang et al (2006) demonstrated that activation of LXR protects against liver injury and dysfunction in a rat model of endotoxemia, in part by exerting an anti-inflammatory effect on Kupffer cells.…”

Section: Discussionmentioning

confidence: 99%

Attenuated mRNA expression of lipid metabolism genes in primary hepatocytes following lipopolysaccharide treatment in dairy cows

Wang¹,

Li²,

Wang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The influence of ruminal acidosis on ruminal microbiology and metabolite production has received considerable attention, but little is known regarding the systemic manifestations that arise from ruminal acidosis. Lipopolysaccharide (LPS) is released in the gastrointestinal tract upon ingestion of high-grain or high-fat diets, and it has been implicated in the etiology of multiple energy-and lipid-related metabolic disturbances in ruminants. The liver plays a crucial role in the acute phase response to intruding pathogens. The effect of blood LPS in subacute ruminal acidosis on lipid metabolism in the liver has not been established. In this study, cell cultures were photographed using an inverted microscope. We observed that hepatocytes changed their morphologies from irregular triangle to circular (contraction) shapes; the number of contracted cells increased with the increasing LPS doses. This suggests that LPS can 3719 Lipid metabolism genes in primary hepatocytes ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 3718-3728 (2015) promote cell contraction and take off the wall, ultimately leading to cell apoptosis. With changes in LPS exposure, hepatocyte number also changes. We explored lipid metabolism in the liver using quantitative reverse transcription-polymerase chain reaction to detect the expression of key lipid metabolism enzymes in hepatocytes. We found that Toll-like receptor 4 signaling pathway mediated by LPS could attenuate mRNA expression of fatty acid synthesis genes and increase the expression of fatty acid transport genes in primary hepatocytes following LPS treatment in dairy cows.

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“…Similar to PPARγ activation, also LXR activation has shown contradictory results regarding its effect on DCs. Next to its effect on DC differentiation [ 60 ], it has been shown to inhibit DC maturation [ 61 , 62 ] as well as sensitize DCs to inflammatory stimuli increasing DC maturation [ 63 ]. Also opposing effects of LXR activation on CCR7 dependent migration have been reported.…”

Section: Nuclear Receptors and Their Ligandsmentioning

confidence: 99%

Microenvironmental derived factors modulating dendritic cell function and vaccine efficacy: the effect of prostanoid receptor and nuclear receptor ligands

Raaijmakers

Ansems

2018

Cancer Immunol Immunother

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Dendritic cells (DCs) are widely used in DC-based immunotherapies because of their capacity to steer immune responses. So far treatment success is limited and more functional knowledge on how DCs initiate and stably drive specific responses is needed. Many intrinsic and extrinsic factors contribute to how DCs skew the immune response towards immunity or tolerance. The origin and type of DC, its maturation status, but also factors they encounter in the in vitro or in vivo microenvironment they reside in during differentiation and maturation affect this balance. Treatment success of DC vaccines will, therefore, also depend on the presence of these factors during the process of vaccination. Identification and further knowledge of natural and pharmacological compounds that modulate DC differentiation and function towards a specific response may help to improve current DC-based immunotherapies. This review focuses on factors that could improve the efficacy of DC vaccines in (pre-)clinical studies to enhance DC-based immunotherapy, with a particular emphasis on compounds acting on prostanoid or nuclear receptor families.

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Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-κBp50

Cited by 13 publications

References 36 publications

MicroRNA-155 Promotes Heat Stress-Induced Inflammation via Targeting Liver X Receptor α in Microglia

MicroRNA-155 Promotes Heat Stress-Induced Inflammation via Targeting Liver X Receptor α in Microglia

Attenuated mRNA expression of lipid metabolism genes in primary hepatocytes following lipopolysaccharide treatment in dairy cows

Microenvironmental derived factors modulating dendritic cell function and vaccine efficacy: the effect of prostanoid receptor and nuclear receptor ligands

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