Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation

  title={Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation},
  author={Concetta Crisafulli and Emanuela Mazzon and Irene Paterniti and Maria Galuppo and Placido Bramanti and Salvatore Cuzzocrea},
  journal={Respiratory Research},
  pages={19 - 19}
BackgroundLiver × receptor α (LXRα) and β (LXRβ) are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse… 

Liver X receptor agonist prevents LPS-induced mastitis in mice.

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

The results suggest that a possible mechanism by which PAF exerts its proinflammatory effect is through the downregulation of LXRα and its related genes, which supports the notion that LXR α ligands exert a modulatory role in the neutrophil‐mediated inflammatory response.

Age-dependent therapeutic effects of liver X receptor-α activation in murine polymicrobial sepsis

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Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

The LXR agonist TO901317 had potent antioxidant, anti-inflammatory, and antiapoptotic effects against PQ-induced ALI, leading to marked cell apoptosis in the lung tissues.

Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling

It is demonstrated that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects.

Liver X Receptor &agr; Activation with the Synthetic Ligand T0901317 Reduces Lung Injury and Inflammation After Hemorrhage and Resuscitation Via Inhibition of the Nuclear Factor &kgr;B Pathway

The data suggest that LXR&agr; is an important modulator of the inflammatory response and lung injury after severe hemorrhagic shock, likely through the inhibition of the nuclear factor &kgr;B pathway.

A Liver-X-Receptor Ligand, T0901317, Attenuates IgE Production and Airway Remodeling in Chronic Asthma Model of Mice

LXR ligand may attenuate the progressing of airway remodeling, providing a potential treatment of asthma.


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Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

Treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors and is associated with the inhibition of nuclear factor-κB (NF-κBs) activation.

Novel Role for the Liver X Nuclear Receptor in the Suppression of Lung Inflammatory Responses*

This study is the first to demonstrate anti-inflammatory actions of LXRs in the lung, and suggests that LXR ligands have utility in the treatment of lung diseases that involves chronic inflammation mediated by macrophages and neutrophils.

Effects of Liver X Receptor Agonist Treatment on Pulmonary Inflammation and Host Defense1

A novel role is defined for LXR in lung pathophysiology and neutrophil biology and pharmacologic activation of LXR is identified as a potential tool for modulation of innate immunity in the lung.

Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis.

Evidence is provided that activation of liver X receptors and retinoid X receptors inhibits apoptotic responses of macrophages to macrophage colony-stimulating factor withdrawal and several inducers of apoptosis, raising the possibility that LXR/RXR agonists may be exploited to enhance innate immunity to bacterial pathogens that induce apoptotic programs as a strategy for evading host responses.

Reciprocal regulation of inflammation and lipid metabolism by liver X receptors

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Liver X receptor agonists inhibit tissue factor expression in macrophages

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The role of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in the regulation of acute inflammation.

The increased inflammatory response observed in PPar-alphaKO mice strongly suggests that a PPAR-alpha pathway modulates the degree of acute inflammation in the mice.

Activation of Liver X Receptors Promotes Neuroprotection and Reduces Brain Inflammation in Experimental Stroke

It is shown that administration of the synthetic LXR agonists GW3965 or TO901317 after the ischemic occlusion improves stroke outcome as shown by decreased infarct volume area and better neurological scores in rats.

Downregulation of liver X receptor-alpha in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines.

It is concluded that the APR suppresses the expression of both nuclear receptors LXRalpha/RXRalpha and several LXR alpha coactivators in kidney, which could be a mechanism for coordinately regulating the expressionof multiple LXR target genes that play important roles in lipid metabolism in kidney during the APR.

Identification of macrophage liver X receptors as inhibitors of atherosclerosis

Elimination of LXR activity in bone marrow-derived cells mimics many aspects of Tangier disease, a human high density lipoprotein deficiency, including aberrant regulation of cholesterol transporter expression, lipid accumulation in macrophages, splenomegaly, and increased atherosclerosis.