Retinoic acid ameliorates low-grade endotoxemia-induced mastitis by limiting inflammatory responses in mice

• Published in: Microbial pathogenesis 2023-12, Vol.185, p.106426-106426, Article 106426
• Main Authors: Wu, Keyi, Shang, Shan, Bao, Lijuan, Zhao, Yihong, Guan, Zhihang, Xu, Jiawen, Sun, Hao, Yuan, Weijie, Fu, Yunhe, Peng, Luyuan, Zhao, Caijun
• Format: Article
• Language: English
• Subjects: Endotoxemia; Inflammatory responses; Mastitis; Retinoic acid (RA)
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2023.106426

Mastitis is a serious disease for humans and animals, which causes huge economic losses in the dairy industry and is hard to prevent due to the complex and unclear pathogenesis. Subacute ruminal acidosis (SARA) has contributed to the development of mastitis by inducing ruminal dysbiosis and subsequent low-grade endotoxemia (LGE), however, how ruminal metabolic changes regulate this progress is still unclear. Our previous study revealed that cows with SARA had increased ruminal retinoic acid (RA) levels, a metabolic intermediate of vitamin A that plays an essential role in mucosal immune responses. Hence, the aim of this study was to investigate the protective effect of RA on LGE-induced mastitis and the underlying mechanisms in mice. The results showed that RA alleviated LGE-induced mastitis, as evidenced by RA significantly reduced the increase in mammary proinflammatory cytokines and improved blood-milk barrier injury caused by LGE. In addition, RA increased the expression of tight junction proteins, including ZO-1, occludin and claudin-3. Furthermore, we found that RA limited the mammary inflammatory responses by inhibiting the activation of NF-κB and NLRP3 signaling pathways. These findings suggest that RA effectively alleviates LGE-induced mastitis and implies a potential strategy for the treatment and prevention of mastitis and other diseases. •Retinoic acid (RA) alleviates low-grade endotoxemia (LGE)-induced mammary injury and proinflammatory cytokines production in mice.•RA improves LGE-induced damage of the blood-milk barrier in mice.•RA alleviates LGE-induced mastitis by inhibiting the activation of mammary NF-κB and NLRP3 signaling pathways.