title: Activation of Liver X Receptor Attenuates Oleic Acid-Induced Acute Respiratory Distress Syndrome.
abstract: Liver X receptors (LXRs) were identified as receptors that sense oxidized cholesterol derivatives. LXRs are best known for their hepatic functions in regulating cholesterol metabolism and triglyceride synthesis, but whether and how LXRs play a role in the lung diseases is less understood. To study the function of LXRs in acute respiratory distress syndrome (ARDS), we applied the oleic acid (OA) model of ARDS to mice whose LXR was genetically or pharmacologically activated. The VP-LXRα knock-in (LXR-KI) mice, in which a constitutively activated LXRα (VP-LXRα) was inserted into the mouse LXRα locus, were used as the genetic gain-of-function model. We showed that the OA-induced lung damages, including the cytokine levels and total cell numbers and neutrophil numbers in the bronchoalveolar lavage fluid, the wet/dry weight ratio, and morphological abnormalities were reduced in the LXR-KI mice and wild-type mice treated with the LXR agonist GW3965. The pulmonoprotective effect of GW3965 was abolished in the LXR-null mice. Consistent with the pulmonoprotective effect of LXR and the induction of antioxidant enzymes by LXR, the OA-induced suppression of superoxide dismutase and catalase was attenuated in LXR-KI mice and GW3965-treated wild-type mice. Taken together, our results demonstrate that activation of LXRs can alleviate OA-induced ARDS by attenuating the inflammatory response and enhancing antioxidant capacity.
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Occupational Disease, Peking University Third Hospital, Beijing, China.
authors: Zanmei
authors: Z
authors: Zhao
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors: Dan
authors: D
authors: Xu
authors: Department of Occupational Disease, Peking University Third Hospital, Beijing, China.
authors: Shuqiang
authors: S
authors: Li
authors: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors: Bei
authors: B
authors: He
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Yixian
authors: Y
authors: Huang
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Meishu
authors: M
authors: Xu
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Songrong
authors: S
authors: Ren
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Song
authors: S
authors: Li
authors: Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors: Hui
authors: H
authors: Wang
authors: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: wex6@pitt.edu.
authors: Wen
authors: W
authors: Xie
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019301:Oleic Acid / Q000009:adverse effects*; D018384:Oxidative Stress; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D001565:Benzoates; D001596:Benzylamines; D016207:Cytokines; C473027:GW 3965; D000071518:Liver X Receptors; D019301:Oleic Acid; D002784:Cholesterol