title: The role of the liver X receptor in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  There is a need for novel anti-inflammatory therapies to treat COPD. The liver X receptor (LXR) is a nuclear hormone receptor with anti-inflammatory properties.
  
  
  METHODS
  We investigated LXR gene and protein expression levels in alveolar macrophages and whole lung tissue from COPD patients and controls, the effect of LXR activation on the suppression of inflammatory mediators from LPS stimulated COPD alveolar macrophages, and the effect of LXR activation on the induction of genes associated with alternative macrophage polarisation.
  
  
  RESULTS
  The levels of LXR mRNA were significantly increased in whole lung tissue extracts in COPD patients and smokers compared to non-smokers. The expression of LXR protein was significantly increased in small airway epithelium and alveolar epithelium in COPD patients compared to controls. No differences in LXR mRNA and protein levels were observed in alveolar macrophages between patient groups. The LXR agonist GW3965 significantly induced the expression of the LXR dependent genes ABCA1 and ABCG1 in alveolar macrophage cultures. In LPS stimulated alveolar macrophages, GW3965 suppressed the production of CXCL10 and CCL5, whilst stimulating IL-10 production.
  
  
  CONCLUSIONS
  GW3965 did not significantly suppress the production of TNFα, IL-1β, or CXCL8. Our major finding is that LXR activation has anti-inflammatory effects on CXC10, CCL5 and IL-10 production from alveolar macrophages.
authors.affiliation: The University of Manchester, NIHR Translational Research Facility, University Hospital of South Manchester Foundation Trust, Southmoor Road, Manchester M23 9LT, UK. Andrew.Higham@postgrad.manchester.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Higham
authors.forename: Simon
authors.initials: S
authors.lastname: Lea
authors.forename: Jonathan
authors.initials: J
authors.lastname: Plumb
authors.forename: Barbara
authors.initials: B
authors.lastname: Maschera
authors.forename: Karen
authors.initials: K
authors.lastname: Simpson
authors.forename: David
authors.initials: D
authors.lastname: Ray
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
mesh_terms: D000368:Aged; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D016022:Case-Control Studies; D016764:Cell Polarity; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D000071518:Liver X Receptors; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism
chemical_list: D001565:Benzoates; D001596:Benzylamines; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; C473027:GW 3965; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D016753:Interleukin-10