Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Department of Cardiology and Nephrology in Second People's Hospital of Chongqing Jiulongpo District, Chongqing, 400052, People's Republic of China.
Inflammation. 2018 Oct;41(5):1912-1921. doi: 10.1007/s10753-018-0834-3.
Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been shown to have anti-inflammatory effect by inhibition of the nuclear factor κB (NF-κB) pathway and is involved in lipopolysaccharide (LPS)-induced inflammation. Cell-death-inducing DFF45-like effector C (CIDEC) can directly down-regulate AMPK activity through interacting with AMPKα subunit. However, whether the AMPK or CIDEC is involved in LPS-induced inflammation in renal tubular epithelial cells is still unknown. Therefore, we studied the role of AMPK and CIDEC in LPS-treated NRK-52E cells. Our results showed that LPS could up-regulate the expression of CIDEC in vitro and in vivo. Silencing CIDEC by CIDEC-siRNA could restore expression of phosphorylated-AMPKα which was decreased by LPS, suppress LPS-induced NF-κB pathway activation, and TNF-α, IL-6, and IL-1β production in NRK-52E cells. Furthermore, silencing CIDEC also partially alleviated LPS-induced epithelial cells apoptosis. In conclusion, the results demonstrated that CIDEC/AMPK signaling pathway played an important role in LPS-induced inflammation and epithelial cells apoptosis.
腺苷 5'-单磷酸激活蛋白激酶 (AMPK) 通过抑制核因子 κB (NF-κB) 途径显示出抗炎作用，并且参与脂多糖 (LPS) 诱导的炎症。细胞死亡诱导 DFF45 样效应因子 C (CIDEC) 可以通过与 AMPKα 亚基相互作用直接下调 AMPK 活性。然而，AMPK 或 CIDEC 是否参与 LPS 诱导的肾小管上皮细胞炎症仍然未知。因此，我们研究了 AMPK 和 CIDEC 在 LPS 处理的 NRK-52E 细胞中的作用。我们的结果表明，LPS 可以在体外和体内上调 CIDEC 的表达。CIDEC-siRNA 沉默 CIDEC 可以恢复 LPS 下调的磷酸化-AMPKα的表达，抑制 LPS 诱导的 NF-κB 途径激活，并抑制 NRK-52E 细胞中 TNF-α、IL-6 和 IL-1β 的产生。此外，沉默 CIDEC 也部分减轻了 LPS 诱导的上皮细胞凋亡。总之，这些结果表明 CIDEC/AMPK 信号通路在 LPS 诱导的炎症和上皮细胞凋亡中起重要作用。
