Simultaneous activation of the liver X receptors (LXR and LXR) drives murine collagen-induced arthritis disease pathology

Asquith, D.L., Miller, A.M., Reilly, J.H., Kerr, S., Welsh, P. , Sattar, N. and McInnes, I.B. (2011) Simultaneous activation of the liver X receptors (LXR and LXR) drives murine collagen-induced arthritis disease pathology. Annals of the Rheumatic Diseases, 70(12), pp. 2225-2228. (doi:10.1136/ard.2011.152652) (PMID:21859686.)

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Publisher's URL: http://dx.doi.org/10.1136/ard.2011.152652

Abstract

Background: It has previously been shown that dual activation of the Liver X Receptors (LXR alpha and LXR beta) by the agonist, GW3965, enhances pathology in a murine model of collagen-induced arthritis. Objective To determine whether LXR alpha or LXR beta have discrete roles in driving articular inflammation.

Methods: Arthritis was induced in male C57BL/6 wild-type (WT), LXR alpha-/-, LXR beta-/- and LXR alpha/beta double KO mice by injection with type II collagen and treated with 30 mg/kg of the LXR agonist GW3965 or vehicle control. The mice were monitored for articular inflammation and cartilage degradation by scoring for clinical signs of arthritis and by histological examination of the joints.

Results: Administration of 30 mg/kg GW3965 significantly increases the severity of arthritis in WT but not LXR alpha-/-, LXR beta-/- or LXR alpha/beta KO mice as assessed by an increase in the clinical score, paw thickness and articular histological analysis.

Conclusion: The proinflammatory effects associated with the administration of GW3965 are mediated specifically through LXRs. The absence of increased disease severity in the LXR alpha-/- and LXR beta-/- GW3965-treated groups shows for the first time that agonism of both LXR alpha and LXR beta is required to drive proinflammatory pathways in vivo.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Reilly, Mr James and Asquith, Dr Darren and Miller, Dr Ashley and Kerr, Mrs Shauna and Welsh, Dr Paul and Sattar, Professor Naveed
Authors: Asquith, D.L., Miller, A.M., Reilly, J.H., Kerr, S., Welsh, P., Sattar, N., and McInnes, I.B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Annals of the Rheumatic Diseases
ISSN:0003-4967
ISSN (Online):1468-2060
Published Online:22 August 2011

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