1. Academic Validation
  2. Urocortin participates in LPS-induced apoptosis of THP-1 macrophages via S1P-cPLA2 signaling pathway

Urocortin participates in LPS-induced apoptosis of THP-1 macrophages via S1P-cPLA2 signaling pathway

  • Eur J Pharmacol. 2020 Nov 15;887:173559. doi: 10.1016/j.ejphar.2020.173559.
Chao Zhu 1 Jun Zhou 2 Tiantian Li 2 Junyu Mu 2 Lai Jin 2 Shengnan Li 3
Affiliations

Affiliations

  • 1 Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, PR China. Electronic address: czhu@njmu.edu.cn.
  • 2 Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, PR China.
  • 3 Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, PR China. Electronic address: snli@njmu.edu.cn.
Abstract

There is little literature showing the effect of urocortin (UCN) on macrophage Apoptosis. The underlying mechanism is also unclear. This work was to investigate the involvement of UCN in the regulation of LPS-induced macrophage Apoptosis and hence in the prevention from the atherosclerotic lesion development through targeting PLA2. Flow cytometry analysis showed that cell Apoptosis was increased by more than 50% after LPS treatment in human THP-1 macrophage. Lp-PLA2 and cPLA2 were found to mediate LPS-induced macrophage Apoptosis and NF-κB differentially influenced the expression of Lp-PLA2 and cPLA2. However, the reverse regulation of the expression of Lp-PLA2 and cPLA2 by NF-κB suggested that NF-κB may not be a key target for regulating macrophage Apoptosis. Interestingly, we found that the approximate three folds upregulation of cPLA2 was in line with the induction of S1P formation and cell Apoptosis by LPS. Inversely, LPS obviously decreased UCN expression by about 50% and secretion by about 25%. Both the Enzyme inhibitor and knockdown expression of cPLA2 could completely abolish LPS-induced cell Apoptosis. In addition, suppression of S1P synthesis by SphK1 Inhibitor PF-543 reduced the expression of cPLA2 and cell Apoptosis but at the same time restored the normal level of UCN in Cell Culture supernatant. Furthermore, addition of exogenous UCN also reversed LPS-induced expression of cPLA2 and Apoptosis. Taken together, UCN may be the reverse regulator of LPS-S1P-cPLA2-apoptosis pathway, thereby contributing to the prevention from the formation of unstable plaques.

Keywords

Apoptosis; LPS; Macrophage; UCN; cPLA2.

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