SIRT7 Regulates Lipopolysaccharide-Induced Inflammatory Injury by Suppressing the NF-κB Signaling Pathway

Area of Science:

• Veterinary immunology
• Molecular biology
• Cellular inflammation

Background:

• Mastitis significantly impacts the global cattle industry, causing reduced dairy production and reproductive issues.
• Current mastitis prevention and treatment strategies remain largely ineffective, highlighting the need for novel therapeutic targets.
• Sirtuin 7 (SIRT7), an NAD+-dependent deacetylase, is implicated in various cellular processes but its role in inflammation is unexplored.

Purpose of the Study:

• To investigate the role of Sirtuin 7 (SIRT7) in the inflammatory response associated with mastitis.
• To determine the potential of SIRT7 as a therapeutic target for mastitis.

Main Methods:

• Dairy cow mammary epithelial cells (DCMECs) were isolated and an in vitro model of lipopolysaccharide (LPS)-induced inflammation was established.
• SIRT7 expression levels were analyzed in both mastitic cattle tissue samples and LPS-treated DCMECs.
• The effects of SIRT7 knockdown and overexpression on inflammatory mediators, signaling pathways (TAK1, NF-κB), and apoptosis were examined.

Main Results:

• SIRT7 expression was found to be downregulated in mastitic cattle tissues and LPS-treated DCMECs.
• SIRT7 knockdown exacerbated LPS-induced inflammation by increasing reactive oxygen and nitric oxide production, upregulating TAB1 and TLR4, and activating the TAK1/NF-κB pathway.
• SIRT7 overexpression demonstrated anti-inflammatory and anti-apoptotic effects in LPS-treated DCMECs, suppressing the NF-κB signaling pathway.

Conclusions:

• SIRT7 plays a crucial role in suppressing lipopolysaccharide (LPS)-induced inflammation and apoptosis in dairy cow mammary epithelial cells (DCMECs) through the NF-κB signaling pathway.
• Downregulation of SIRT7 is associated with increased inflammation in mastitis.
• SIRT7 represents a promising pharmacological target for the clinical treatment of mastitis.