PMID- 32572902
OWN - NLM
STAT- MEDLINE
DCOM- 20210421
LR  - 20210421
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 11
DP  - 2020 Jun
TI  - Sirt1 suppresses MCP-1 production during the intervertebral disc degeneration by 
      inactivating AP-1 subunits c-Fos/c-Jun.
PG  - 5895-5904
LID - 21482 [pii]
LID - 10.26355/eurrev_202006_21482 [doi]
AB  - OBJECTIVE: The anti-inflammatory effect of Sirtuin 1 (Sirt1) during 
      intervertebral disc degeneration (IDD) has been widely confirmed. Monocyte 
      chemoattractant protein-1 (MCP-1) activation is the initiating inflammatory 
      response associated with the IDD. However, whether Sirt1 suppresses MCP-1 in the 
      intervertebral disc is unclear. PATIENTS AND METHODS: The MCP-1 and Sirt1 protein 
      expression in the degenerated and non-degenerated NP tissues were compared by 
      immunohistochemistry (IHC). We induced nucleus pulposus (NP) cell degeneration by 
      IL-1beta and mediated cellular Sirt1 expression through the Sirt1 activator 
      resveratrol (Res) or inhibitor Nicotinamide (Nico). In addition, the inhibitors 
      of MCP-1 and Activator protein 1 (AP-1) were also used in cell culture. The 
      function of NP cells was determined by the type II collagen and Cell Counting 
      Kit-8 (CCK-8) assay. We assessed the Sirt1 and MCP-1 expression by the Reverse 
      Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). The AP-1 activity 
      was valued by the phosphorylation of its components c-Fos, and c-Jun. RESULTS: 
      Both in vivo and in vitro experimental results indicated that MCP-1 was 
      upregulated in the degenerated condition, which was opposite to Sirt1 expression. 
      Res suppressed AP-1, the phosphorylation of c-Fos/c-Jun, and the MCP-1 
      expression. On the contrary, Sirt1 downregulation by Nico aggravated the 
      phosphorylation of c-Fos/c-Jun and MCP-1 expression. However, the MCP-1 
      suppression did not affect the Sirt1 and AP-1 levels. The destruction of AP-1 
      activation also inhibited MCP-1 expression but not Sirt1. The upregulation of 
      Sirt1 and suppression of MCP-1 improved the type II collagen expression and cell 
      viability, which was injured by IL-1beta. CONCLUSIONS: Sirt1 suppresses the MCP-1 
      production in the degenerated NP cells by suppressing the phosphorylation of the 
      AP-1 subunits c-Fos and c-Jun.
FAU - Cai, W-T
AU  - Cai WT
AD  - Department of Spinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital 
      of Hainan Medical University, Haikou, China. cwt7724@126.com.
FAU - Guan, P
AU  - Guan P
FAU - Lin, M-X
AU  - Lin MX
FAU - Fu, B
AU  - Fu B
FAU - Wu, B
AU  - Wu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (IL1B protein, human)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Cell Line
MH  - Cell Survival
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - Intervertebral Disc Degeneration/*metabolism/pathology
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-fos/*metabolism
MH  - Proto-Oncogene Proteins c-jun/*metabolism
MH  - Sirtuin 1/genetics/*metabolism
EDAT- 2020/06/24 06:00
MHDA- 2021/04/22 06:00
CRDT- 2020/06/24 06:00
PHST- 2020/06/24 06:00 [entrez]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2021/04/22 06:00 [medline]
AID - 21482 [pii]
AID - 10.26355/eurrev_202006_21482 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):5895-5904. doi: 
      10.26355/eurrev_202006_21482.