Sodium butyrate reduces bovine mammary epithelial cell inflammatory responses induced by exogenous lipopolysaccharide, by inactivating NF-κB signaling
Sodium butyrate reduces bovine mammary epithelial cell inflammatory responses induced by exogenous lipopolysaccharide, by inactivating NF-κB signaling
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DOI：
10.3168/jds.2020-18189
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发表时间：
2020-09-01
影响因子：
3.5
通讯作者：
Xu, Chuang
中科院分区：
文献类型：
--
作者：
Sun, Xudong;Luo, Shengbin;Xu, Chuang
在应激期，如围产期或病原体攻击期间，分解代谢状态的外源分子(如脂肪酸、β-羟丁酸)[如脂多糖(LPS)]可在肝脏和乳腺等组织中引发炎症反应。丁酸盐是瘤胃中产生的主要短链脂肪酸之一，在非反刍动物身上的研究表明，它可以改变炎症过程。本研究的主要目的是探讨丁酸钠对脂多糖诱导的牛乳腺上皮细胞炎症的预防作用及其分子机制。用SB(0.1、0.25、0.5、1、2或5 mM)或组蛋白去乙酰化酶抑制剂曲古抑素A(TSA；6.25、12.5、25或50 nM)处理永生化牛乳腺上皮细胞(MAC-T)18h，然后再用1mU g/mLLPS刺激6h。内毒素可上调肿瘤坏死因子α(TNFA)、白介素6(IL6)和白介素1B(IL1B)的mRNA表达，而TSA抑制组蛋白脱乙酰酶可抑制这一作用。更重要的是，SB通过阻止TNFA、IL6和IL1B的上调，对炎症反应有明显的剂量依赖效应。此外，TSA或SB可减弱脂多糖对组蛋白H3乙酰化蛋白丰度的下调作用。SB可减弱LPS引起的p-I-kappa Bα/I-kappa Bα比值和p-p65/p65蛋白丰度的增加以及核定位的增加。总体而言，数据表明，外源性Sb减轻乳腺细胞的促炎反应，部分是通过翻译后机制，减少核因子-kappa B信号。因此，SB对炎症挑战的细胞保护作用可能是一种预防工具，有助于乳腺抵御病原体，如引起乳房炎的病原体。
Exogenous molecules derived from catabolic states (e.g., fatty acids, beta-hydroxybutyrate) during periods of stress such as the periparturient period or pathogen challenges [e.g., lipopolysaccharide (LPS)] can trigger an inflammatory response in tissues such as the liver and the mammary gland. Butyrate is one of the major short-chain fatty acids produced in the rumen, and work with non-ruminants has demonstrated that it can alter inflammatory processes. The primary objective of this study was to explore the preventive effect of sodium butyrate (SB) on LPS-induced inflammation in bovine mammary epithelial cells along with underlying molecular mechanisms. Immortalized bovine mammary epithelial cells (MAC-T) were treated with SB (0.1, 0.25, 0.5, 1, 2, or 5 mM) or with the histone deacetylase inhibitor trichostatin A (TSA; 6.25, 12.5, 25, or 50 nM) for 18 h, followed by a challenge with 1 mu g/mL LPS for an additional 6 h. Pretreatment with SB prevented increase in apoptosis of LPS-challenged MAC-T cells in a dose-dependent manner. The LPS treatment up-regulated mRNA abundance of tumor necrosis factor alpha (TNFA), interleukin-6 (IL6), and interleukin-1B (IL1B), whereas inhibition of histone deacetylase with TSA dampened this effect. More importantly, SB had clear dose-dependent effects on the inflammatory response by preventing upregulation of TNFA, IL6, and IL1B. Furthermore, pretreatment with TSA or SB attenuated the downregulation of histone H3 acetylation protein abundance induced by LPS. The greater ratio of p-I kappa B alpha/I kappa B alpha and p-p65/p65 protein abundance and the increase in nuclear localization of NF-kappa B p65 protein in response to LPS were attenuated by pretreatment with SB. Overall, the data indicated that exogenous SB alleviates mammary cell pro-inflammatory responses partly through post-translational mechanisms that diminish NF-kappa B signaling. Thus, the cytoprotective effect of SB against an inflammatory challenge might represent a preventive tool to help the mammary gland against pathogens such as those causing mastitis.