PMID- 32655974 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1598-2629 (Print) IS - 2092-6685 (Electronic) IS - 1598-2629 (Linking) VI - 20 IP - 3 DP - 2020 Jun TI - Cereblon Deletion Ameliorates Lipopolysaccharide-induced Proinflammatory Cytokines through 5'-Adenosine Monophosphate-Activated Protein Kinase/Heme Oxygenase-1 Activation in ARPE-19 Cells. PG - e26 LID - 10.4110/in.2020.20.e26 [doi] LID - e26 AB - 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-kappaB p65 and activation of NF-kappaB 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. CI - Copyright (c) 2020. The Korean Association of Immunologists. FAU - Kim, Yun Kyu AU - Kim YK AUID- ORCID: 0000-0002-8403-945X AD - Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea. FAU - Chae, Soo Chul AU - Chae SC AD - Department of Integrative Medical Sciences, Nambu University, Gwangju 62271, Korea. AD - Department of Life Science, Hanyang University, Seoul 04763, Korea. FAU - Yang, Hun Ji AU - Yang HJ AD - Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea. FAU - An, Da Eun AU - An DE AD - Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea. FAU - Lee, Sion AU - Lee S AD - Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea. FAU - Yeo, Myeong Gu AU - Yeo MG AD - Department of Integrative Medical Sciences, Nambu University, Gwangju 62271, Korea. FAU - Lee, Kyung Jin AU - Lee KJ AUID- ORCID: 0000-0002-5282-5683 AD - Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea. AD - Department of Life Science, Hanyang University, Seoul 04763, Korea. LA - eng PT - Journal Article DEP - 20200625 PL - Korea (South) TA - Immune Netw JT - Immune network JID - 101137270 PMC - PMC7327155 OTO - NOTNLM OT - AMP-activated protein kinase OT - Cereblon OT - Cytokines OT - Heme oxygenase-1 OT - Inflammation OT - Retina COIS- Conflicts of Interest: The authors declare no potential conflicts of interest. EDAT- 2020/07/14 06:00 MHDA- 2020/07/14 06:01 PMCR- 2020/06/01 CRDT- 2020/07/14 06:00 PHST- 2020/03/26 00:00 [received] PHST- 2020/06/19 00:00 [revised] PHST- 2020/06/20 00:00 [accepted] PHST- 2020/07/14 06:00 [entrez] PHST- 2020/07/14 06:00 [pubmed] PHST- 2020/07/14 06:01 [medline] PHST- 2020/06/01 00:00 [pmc-release] AID - 2020200307 [pii] AID - 10.4110/in.2020.20.e26 [doi] PST - epublish SO - Immune Netw. 2020 Jun 25;20(3):e26. doi: 10.4110/in.2020.20.e26. eCollection 2020 Jun.