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Open Access Highly Accessed Research

The role of the liver X receptor in chronic obstructive pulmonary disease

Andrew Higham1*, Simon Lea1, Jonathan Plumb1, Barbara Maschera2, Karen Simpson2, David Ray1 and Dave Singh1

Author Affiliations

1 The University of Manchester, NIHR Translational Research Facility, University Hospital of South Manchester Foundation Trust, Southmoor Road, Manchester M23 9LT, UK

2 GlaxoSmithKline, Respiratory CEDD, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK

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Respiratory Research 2013, 14:106  doi:10.1186/1465-9921-14-106

Published: 12 October 2013

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.

Keywords:
COPD; Liver X receptor; Alveolar macrophage; Inflammatory cytokines