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Nrf2 Activation and NF-Kb & caspase/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells

Molecular Immunology, ISSN: 0161-5890, Vol: 148, Page: 54-67
2022
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MicroRNA miR-223 modulates NLRP3 and Keap1, mitigating lipopolysaccharide-induced inflammation and oxidative stress in bovine mammary epithelial cells and murine mammary glands

Abstract Bovine mastitis, the most prevalent and costly disease in dairy cows worldwide, decreases milk quality and quantity, and increases cow culling. However, involvement of

Article Description

Mastitis, an inflammation of the mammary gland, is a complex disease that affects the health of dairy cows worldwide. Sodium butyrate (SB) is a short-chain fatty acid that has recently been shown to have antioxidant, anti-inflammatory and anti-apoptotic potential in various cells types, although its role in bovine mammary epithelial cells (bMECs) has not been comprehensively reported. Therefore, the aim of this study was to assess the protective effect of sodium butyrate on Lipopolysaccharide (LPS)-induced mastitis model in vitro and to elucidate the possible underlying molecular mechanisms. The in vitro mastitis model was designed to investigate the regulatory effect of SB on LPS-induced inflammatory conditions in bMECs, with particular emphasis on oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. The results showed that SB co-treatment markedly prevented LPS-induced death of bMECs in a concentration-dependent manner. In addition, SB attenuated LPS-induced oxidative stress (OS) (Increased Intracellular ROS, MDA, and decreased SOD, GSH-Px and CAT activity), thereby reduced inflammation (increased expression of IL-6, IL-Iβ, and TNF-α), and apoptosis (Increased the expression of caspases and Bax and decreased Bcl-2) via inhibiting NF-kB and caspase/bax signaling pathways. Furthermore, the protective effect of SB was also associated with the activation of endogenous antioxidant system (Nrf2, Keap1, NQO-1 and HO-1). Nrf2 silencing significantly abolished the protective effect of SB on bMECs. In conclusion, our findings suggest that SB has a significant protective effect on LPS-induced OS, inflammatory responses and apoptosis by activating Nrf2 and inhibiting NF-kB and ROS-mediated mitochondrial dysfunction. These results propose that SB may be an important regulator of OS and its subsequent inflammatory responses, and thus could be used as a therapeutic agent for bovine mastitis.

Bibliographic Details

Ali, Ilyas; Li, Chengmin; Kuang, Meqian; Shah, Abid Ullah; Shafiq, Muhammad; Ahmad, Muhammad Arslan; Abdalmegeed, Dyaaaldin; Li, Lian; Wang, Genlin

Elsevier BV

Immunology and Microbiology; Biochemistry, Genetics and Molecular Biology

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