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

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.

Combination of resolvin E1 and lipoxin A4 promotes the resolution of pulpitis by inhibiting NF‐κB activation through upregulating sirtuin 7 in dental pulp fibroblasts

“…These results are similar to those of well‐established studies in cardiovascular disease and vascular cells 30,31 . Particularly, our results also demonstrated expression of SIRT7 decreased in pulpitis and was consistent with a recent report regarding mastitis, 54 in which activation of NF‐κB was increased as well, but in which the relationship of SIRT7 and NF‐κB remained unclear. Combined use of RvE1 and LXA4 could strongly increase the NAD+/NADH ratio (Figure 2A), resulting in marked elevation of the expression of the deacetylases SIRT1, SIRT6 and SIRT7 at the mRNA and protein levels, even to well above their levels in the control group (Figure 2B–D,F).…”

p53 inhibition attenuates cisplatin-induced acute kidney injury through microRNA-142-5p regulating SIRT7/NF-κB

“…Moreover, SIRT7 knockdown promotes the translocation of NF-κB p-p65 to the cell nucleus and then increases the secretion of inflammatory cytokines. SIRT7 could suppress LPS-induced inflammation and apoptosis via the NF-κB signaling pathway [ 41 ]. NF-κB is an important transcription factor involved in inflammatory response, cell proliferation, and apoptotic processes in cells [ 42 ].…”

Integration of protein context improves protein- based COVID-19 patient stratification

“…MTTP stimulates phosphatidylcholine transport 47 . Alpha-2macroglobulin (A2M) in uences cytokines signaling 48 , and SIRT7 suppresses in ammation 49 . Since network degree suggests the co-expression associations with other proteins, the network degree changes of these proteins also uncorvered systematic molecular changes in severe cases.…”