Immune Netw.  2020 Jun;20(3):e26. 10.4110/in.2020.20.e26.

Cereblon Deletion Ameliorates Lipopolysaccharide-induced Proinflammatory Cytokines through 5′-Adenosine Monophosphate-Activated Protein Kinase/Heme Oxygenase-1 Activation in ARPE-19 Cells

• Kim YK
• Chae SC
• Yang HJ
• An DE
• Lee S
• Yeo MG
• Lee KJ

• KMID: 2504720
• DOI: http://doi.org/10.4110/in.2020.20.e26

Abstract

Cereblon (CRBN), a negative modulator of AMP-activated protein kinase (AMPK), is highly expressed in the retina. We confirmed the expression of CRBN in ARPE-19 human retinal cells by Western blotting. We also demonstrated that CRBN knock-down (KD) could effectively downregulate IL-6 and MCP-1 protein and gene expression in LPS-stimulated ARPE-19 cells. Additionally, CRBN KD increased the phosphorylation of AMPK/acetyl-coenzyme A carboxylase (ACC) and the expression of heme oxygenase-1 (HO-1) in ARPE-19 cells. Furthermore, CRBN KD significantly reduced LPS-induced nuclear translocation of NF-κB p65 and activation of NF-κB promoter activity. However, these processes could be inactivated by compound C (inhibitor of AMPK) and zinc protoporphyrin-1 (ZnPP-1; inhibitor of HO-1). In conclusion, compound C and ZnPP-1 can rescue LPS-induced levels of proinflammatory cytokines (IL-6 and MCP-1) in CRBN KD ARPE-19 cells. Our data demonstrate that CRBN deficiency negatively regulates proinflammatory cytokines via the activation of AMPK/HO-1 in the retina.

Keyword

AMP-activated protein kinase; Cereblon; Cytokines; Heme oxygenase-1; Inflammation; Retina