PMID- 29738371 OWN - NLM STAT- MEDLINE DCOM- 20190612 LR - 20190613 IS - 1533-4023 (Electronic) IS - 0160-2446 (Linking) VI - 72 IP - 1 DP - 2018 Jul TI - ApoA-1 Mimetic Peptide ELK-2A2K2E Decreases Inflammatory Factor Levels Through the ABCA1-JAK2-STAT3-TTP Axis in THP-1-Derived Macrophages. PG - 60-67 LID - 10.1097/FJC.0000000000000594 [doi] AB - OBJECTIVE: The aim of this study was to determine whether the apolipoprotein A-1 (apoA-1) mimetic peptide ELK-2A2K2E regulates inflammatory cytokine expression through activating the adenosine triphosphate-binding cassette transporter A1 (ABCA1)-janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3)-tristetraprolin (TTP) signaling pathway in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: The cells were treated with the apoA-1 mimetic peptide ELK-2A2K2E at different concentrations (0, 20, 40, and 80 mug/mL) or incubated with ELK-2A2K2E (40 mug/mL) for different times (0, 6, 12, and 24 hours). Our results showed that the levels of the cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were decreased at both concentration- and time-dependent manners. When the cells were exposed to lipopolysaccharides and actinomycin D, ELK-2A2K2E significantly decreased the mRNA stability of inflammatory cytokines at different time points (0, 30, 60, and 120 minutes) by increasing TTP expression as analyzed by real-time quantitative polymerase chain reaction. The effect of ELK-2A2K2E on TTP was obviously blocked by the inhibition of the JAK-STAT3 pathway. Furthermore, we found that ELK-2A2K2E activated the JAK-STAT3-TTP pathway through the upregulation of ABCA1 and then decreased inflammatory cytokine expression. CONCLUSIONS: ApoA-I mimetic peptide ELK-2A2K2E increases the degradation of TNF-alpha, IL-6, and MCP-1 mRNA and reduces the levels of inflammatory cytokines through activating the JAK2-STAT3-TTP signaling pathway that is dependent on the upregulation of ABCA1. FAU - Wang, Jia-Lin AU - Wang JL AD - Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. AD - Department of Cardiology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province, China. AD - Department of Cardiology, the First Affiliated Hospital, University of South China, Hengyang, China. FAU - Gong, Duo AU - Gong D AD - Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Hu, Xin-Yan AU - Hu XY AD - Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Wu, Su AU - Wu S AD - Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Zheng, Xi-Long AU - Zheng XL AD - Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Health Sciences Center, Calgary, Alberta, Canada. FAU - Wu, Jie AU - Wu J AD - Department of Cardiology, the First Affiliated Hospital, University of South China, Hengyang, China. FAU - Tang, Xiao-Er AU - Tang XE AD - Department of Pathology, Shaoyang University, Shaoyang, China. FAU - Zhang, Da-Wei AU - Zhang DW AD - Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta, Alberta, Canada. FAU - Tang, Chao-Ke AU - Tang CK AD - Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (ABCA1 protein, human) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Apolipoprotein A-I) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Oligopeptides) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (Tristetraprolin) RN - 0 (ZFP36 protein, human) RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - ATP Binding Cassette Transporter 1/*metabolism MH - Anti-Inflammatory Agents/*pharmacology MH - Apolipoprotein A-I/*pharmacology MH - Cytokines/genetics/*metabolism MH - Dose-Response Relationship, Drug MH - Down-Regulation MH - Foam Cells/*drug effects/metabolism MH - Humans MH - Inflammation Mediators/*metabolism MH - Janus Kinase 2/*metabolism MH - Molecular Mimicry MH - Oligopeptides/*pharmacology MH - STAT3 Transcription Factor/*metabolism MH - Signal Transduction/drug effects MH - THP-1 Cells MH - Time Factors MH - Tristetraprolin/*metabolism EDAT- 2018/05/09 06:00 MHDA- 2019/06/14 06:00 CRDT- 2018/05/09 06:00 PHST- 2018/05/09 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2018/05/09 06:00 [entrez] AID - 10.1097/FJC.0000000000000594 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2018 Jul;72(1):60-67. doi: 10.1097/FJC.0000000000000594.