Abstract
The liver-X-receptors have shown anti-inflammatory ability in several animal models of respiratory disease. Our purpose is to investigate the effect of LXR ligand in allergen-induced airway remodeling in mice. Ovalbumin-sensitized mice were chronically challenged with aerosolized ovalbumin for 8 weeks. Some mice were administered a LXR agonist, T0901317 (12.5, 25, 50 mg/kg bodyweight) before challenge. Then mice were evaluated for airway inflammation, airway hyperresponsiveness and airway remodeling. T0901317 failed to attenuate the inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid. But the application of T0901317 reduced the thickness of airway smooth muscle and the collagen deposition. Meanwhile, T0901317 treatment evidently abolished the high level of OVA-specific IgE, TGF-β1 and MMP-9 in lung. So LXRs may attenuate the progressing of airway remodeling, providing a potential treatment of asthma.
Highlights
Liver X receptors (LXRa/NR1H3 and LXRb/NR1H2) are members of the nuclear receptor family that play central roles in cholesterol metabolism through controlling the transcription of genes such as ATP-binding cassette A1 (ABCA1) [1,2,3]
Asthma is one of the most common chronic diseases worldwide. It is considered an allergic disease with characteristic airway inflammation and airway remodeling
In this study we evaluate the effect of LXRs on airway remodeling using a long-term exposure murine model of asthma
Summary
Liver X receptors (LXRa/NR1H3 and LXRb/NR1H2) are members of the nuclear receptor family that play central roles in cholesterol metabolism through controlling the transcription of genes such as ATP-binding cassette A1 (ABCA1) [1,2,3]. LXRa is highly expressed in the liver and at lower levels in lung, glands, intestine and kidney, whereas LXRb is ubiquitously expressed. Bronchial asthma is an allergic disease manifests as symptoms such as wheezing, breathlessness, chest tightness and coughing. LXR showed therapeutic roles in murine model of allergic contact dermatitis [13]. These suggest that LXRs are potential targets in asthma prevention and treatment
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