Kynurenic acid protects against mastitis in mice by ameliorating inflammatory responses and enhancing blood-milk barrier integrity
Kynurenic acid protects against mastitis in mice by ameliorating inflammatory responses and enhancing blood-milk barrier integrity
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DOI：
10.1016/j.molimm.2021.06.022
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发表时间：
2021-07-08
影响因子：
3.6
通讯作者：
Hu，Xiaoyu
中科院分区：
文献类型：
--
作者：
Zhao，Caijun;Wu，Keyi;Hu，Xiaoyu
乳腺炎是人类和动物最严重的疾病之一，特别是在现代乳品工业中。寻求安全有效的乳腺炎预防策略是迫切的，因为尽管抗生素有助于控制乳腺炎，但牛奶中的食品安全和药物残留仍然是一个巨大的问题。犬尿氨酸（KYNA），来源于色氨酸代谢的犬尿氨酸途径，已被证明在许多疾病中表现出抗炎和免疫调节作用。最近，据报道，受损的KYNA水平与乳腺炎有关。然而，KYNA在乳腺炎中的生理作用尚未阐明。因此，本研究的目的是研究KYNA在病原体诱导的小鼠乳腺炎中的保护作用，以及这种作用的潜在机制。我们首先评估KYNA对小鼠中LPS诱导的乳腺炎的作用。此外，在乳腺上皮细胞（MMECs）中研究了KYNA的潜在抗炎机制。此外，我们还研究了KYNA对S的影响。aureusandE.大肠杆菌诱导的小鼠乳腺炎。我们的研究结果表明，KYNA减轻LPS诱导的乳腺炎，通过减少炎症反应和增强血-乳屏障的完整性。其作用机制可能与抑制NF-κB和激活Nrf 2/Ho-1有关，这可能是由G蛋白偶联受体35介导的，而不是由芳香烃受体介导的。值得注意的是，KYNA还保护免受S。aureusandE.大肠杆菌诱导的小鼠乳腺炎。总之，我们的研究结果突出了KYNA在乳腺炎中的作用，并作为使用内源性代谢物作为疾病干预的新型预防或治疗策略的基础。
Mastitis is one of the most serious diseases in humans and animals, especially in the modern dairy industry. Seeking safe and effective mastitis prevention strategies is urgent since food safety and drug residues in milk remain an enormous concern, despite the contribution of antibiotics to control mastitis. Kynurenic acid (KYNA), derived from the kynurenine pathway of tryptophan metabolism, has been shown to exhibit anti-inflammatory and immunomodulatory effects in many diseases. Recently, it was reported that impaired KYNA levels were associated with mastitis. However, the physiological role of KYNA in mastitis has not yet been elucidated. Therefore, the aim of this study was to investigate the protective role of KYNA in pathogen-induced mastitis in mice, as well as the underlying mechanism of this effect. We first evaluated the effects of KYNA on LPS-induced mastitis in mice. Additionally, the underlying anti-inflammatory mechanism of KYNA was investigated in mammary epithelial cells (MMECs). Furthermore, we examined the effects of KYNA onS. aureusandE. coliinduced mastitis in mice. Our results demonstrated that KYNA alleviated LPS-induced mastitis by reducing inflammatory responses and enhancing blood-milk barrier integrity. The fundamental mechanisms involved the inhibition of NF-κB and activation of Nrf2/Ho-1, which is probably mediated by G protein-coupled receptor 35 but not aryl hydrocarbon receptor. Notably, KYNA also protected againstS. aureusandE. coliinduced mastitis in mice. In conclusion, our results highlight the role of KYNA in mastitis and serve as a basis for using endogenous metabolite as a novel preventative or therapeutic strategy for disease intervention.