Liver X receptor agonist prevents LPS-induced mastitis in mice

Liver X receptor-alpha (LXR-alpha) which belongs to the nuclear receptor superfamily, is a ligand-activated transcription factor. Best known for its ability to regulate lipid metabolism and transport, LXRs have recently also been implicated in regulation of inflammatory response. The aim of this study was to investigate the preventive effects of synthetic LXR-alpha agonist T0901317 on LPS-induced mastitis in mice. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. T0901317 was injected 1 h before and 12 h after induction of LPS intraperitoneally. The results showed that T0901317 significantly attenuated the infiltration of neutrophilic granulocytes, and the activation of myeloperoxidase (MPO); down-regulated the level of pro-inflammatory mediators including TNF-alpha, IL-1 beta, IL-6, COX-2 and PEG(2); inhibited the phosphorylation of IKB-alpha and NF-kappa B p65, caused by LPS. Moreover, we report for the first time that LXR-alpha activation impaired LPS-induced mastitis. Taken together, these data indicated that T0901317 had protective effect on mastitis and the anti-inflammatory mechanism of T0901317 on LPS induced mastitis in mice may be due to its ability to inhibit NF-kappa B signaling pathway. LXR-alpha activation can be used as a therapeutic approach to treat mastitis. (C) 2014 Elsevier B.V. All rights reserved.