Sirt1 suppresses MCP-1 production during the intervertebral disc degeneration by inactivating AP-1 subunits c-Fos/c-Jun.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES(2020)
摘要
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 (INC). We induced nucleus pulposus (NP) cell degeneration by IL-1p 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 AP1, the phosphorylation of c-Fos/c-Jun, and the MCP-1 expression. On the contrary, Sirt1 down-regulation 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-1 beta. CONCLUSIONS: Sirt1 suppresses the MCP-1 production in the degenerated NP cells by suppressing the phosphorylation of the AP-1 sub-units c-Fos and c-Jun.
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关键词
Intervertebral disc degeneration,Sirt1,MCP-1,AP-1,c-Fos,c-Jun
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