Liver X receptor agonist prevents LPS-induced mastitis in mice
Liver X receptor agonist prevents LPS-induced mastitis in mice
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DOI：
10.1016/j.intimp.2014.07.015
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发表时间：
2014-10-01
影响因子：
5.6
通讯作者：
Zhang, Naisheng
中科院分区：
文献类型：
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作者：
Fu, Yunhe;Tian, Yuan;Zhang, Naisheng
肝X受体α (Liver X receptor-alpha, LXR-alpha)是一种配体激活的转录因子，属于核受体超家族。LXRs以其调节脂质代谢和转运的能力而闻名，最近也被认为与炎症反应的调节有关。本研究旨在探讨合成lxr - α激动剂T0901317对lps诱导小鼠乳腺炎的预防作用。通过乳腺导管注射LPS，建立小鼠乳腺炎模型。在LPS诱导前1 h和诱导后12 h分别腹腔注射T0901317。结果表明：T0901317能显著降低中性粒细胞的浸润，降低髓过氧化物酶（MPO）的活性；下调促炎介质tnf - α、IL-1 β、IL-6、COX-2、PEG水平(2)；抑制LPS引起的ikb - α和nf - κ B p65的磷酸化。此外，我们首次报道lxr - α激活会损害lps诱导的乳腺炎。综上所述，这些数据表明T0901317对乳腺炎具有保护作用，T0901317对LPS诱导小鼠乳腺炎的抗炎机制可能与抑制NF-kappa B信号通路有关。lxr - α激活可以作为治疗乳腺炎的一种治疗方法。(C) 2014 Elsevier B.V.版权所有
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.