Rac1 signaling regulates LPS-induced mouse mastitis via inhibition of NLRP3, NF-κB and MAPK signaling pathways

Abstract Background Bovine mastitis characterized by mammary gland inflammatory responses, is the most frequent and costly diseases in dairy cattle. Researchers have been seeking effective treatments for this disease, but still not very successful. Ras-related C3 botulinum toxin substrate 1 (Rac1) is implicated in various cellular functions, including apoptosis, ROS production and inflammatory responses, and presents an attractive therapeutic target for many diseases. However, the effects of Rac1 signaling on mastitis remain unclear. The aim of this study is to investigate the effects of Rac1 signaling on mastitis via inhibition by Rac1 specific inhibitor NSC23766 based on a murine model of lipoplysaccharide (LPS)-induced mastitis. Methods Murine mastitis model was established by perfusion of LPS, hematoxylin-eosin (H & E) staining was employed to explore the mechanisms in mouse model, qRT- PCR analysis, Western blotting analysis. Results The results revealed that NSC23766 significantly decreased the damage of mammary gland by LPS, reduced myeloperoxidase activities, and the productions of IL-1β, IL-6, TNF-α and MCP-1 gene expression in the mammary glands with LPS perfusion. Moreover, western blot analysis showed that NSC23766 inhibited the phosphoryation of p65, IκBα, ERK, and p38, and suppressed the expression of NLRP3. Conclusion These findings suggested that administration of NSC23766 prevented the development of mastitis by inhibiting NLRP3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Accordingly, this study may provide research basis for the development of new drugs against mastitis, and NSC23766 might be a potential therapeutic drugs for mastitis.