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

Kun-Lin Chen,Lian Li,Fang-Xiao Yang,Mei-Qian Kuang,Cheng-Min Li,Gen-Lin Wang,Yi-Ru Wang

doi:10.1155/2019/3187972

Kun-Lin Chen, Lian Li + Show 5 more

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https://doi.org/10.1155/2019/3187972

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Abstract

Mastitis has severely affected the cattle industry worldwide and has resulted in decreased dairy production and cattle reproduction. Although prevention and treatment methods have been implemented for decades, cattle mastitis is still an intractable disease. Sirtuin 7 (SIRT7) is an NAD+-dependent deacetylase that is involved in various biological processes, including ribosomal RNA synthesis and protein synthesis, DNA damage response, metabolism, and tumorigenesis. However, whether SIRT7 participates in inflammation remains unknown. Our results revealed that SIRT7 is downregulated in tissue samples from mastitic cattle. Therefore, we isolated dairy cow mammary epithelial cells (DCMECs) from breast tissues and developed an in vitro model of lipopolysaccharide- (LPS-) induced inflammation to examine SIRT7 function and its potential role in inflammation. We showed that SIRT7 was significantly downregulated in LPS-treated DCMECs. SIRT7 knockdown significantly increased the LPS-stimulated production of inflammatory mediators, like reactive oxygen and nitric oxide, and upregulated TAB1 and TLR4. In addition, SIRT7 knockdown significantly increased the phosphorylation of TAK1 and NF-κBp65 in LPS-treated DCMECs. Moreover, SIRT7 knockdown promoted the translocation of NF-κBp-p65 to the cell nucleus and then increased the secretion of inflammatory cytokines (IL-1β and IL-6). In contrast, SIRT7 overexpression had the opposite effects when compared to SIRT7 knockdown in LPS-treated DCMECs. In addition, SIRT7 overexpression attenuated LPS-induced DCMEC apoptosis. Taken together, our results indicate that SIRT7 can suppress LPS-induced inflammation and apoptosis via the NF-κB signaling pathway. Therefore, SIRT7 may be considered as a potential pharmacological target for clinical mastitis therapy.

Highlights

Clinical mastitis (CM) is a widespread and economically important disease that affects dairy cattle by reducing milk quality and production
Sirtuin 7 (SIRT7) was significantly downregulated in the five tissue samples from mastitis cattle as compared to that in normal samples (Figure 1(a))
SIRT7 mRNA and protein expression were significantly downregulated in LPS-treated dairy cow mammary epithelial cells (DCMECs) relative to that in control cells after 6 h treatment (Figures 1(c)–1(f))

Summary

Introduction

Clinical mastitis (CM) is a widespread and economically important disease that affects dairy cattle by reducing milk quality and production. The major outer membrane component of E. coli is lipopolysaccharide (LPS), which activates the TLR4-NF-κB signaling pathway, stimulating the release of inflammatory cytokines [6]. These cytokines and mediators further aggravate the pathology and inflammatory responses involved in mastitis. Mastitis is characterized by increased secretion of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, which have been demonstrated to direct the migration of neutrophils to the site of infection [7]. Exposing neutrophils and macrophages to LPS rapidly induces the secretion of many mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and reactive oxygen species (ROS) [8].

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