PMID- 30513452 OWN - NLM STAT- MEDLINE DCOM- 20190430 LR - 20190430 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 105 DP - 2019 Jan TI - Nrf2/ARE pathway inhibits inflammatory infiltration by macrophage in rats with autoimmune myositis. PG - 165-172 LID - S0161-5890(18)30578-9 [pii] LID - 10.1016/j.molimm.2018.11.014 [doi] AB - BACKGROUND: Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by muscle disorders. We conducted this study to detect whether NF-E2-related factor 2 (Nrf2) pathway inhibit inflammatory infiltration by macrophage in experimental autoimmune myositis (EAM) rat model. METHODS: CD163 levels were examined by immunohistochemistry (IHC), while serum creatine kinase (CK), reactive oxygen species (ROS), and serum monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) levels were determined by enzyme linked immunosorbnent assay (ELISA), both in IIM patients and EAM rat. We also detected MCP-1, TNF-alpha, IL-6, and Nrf2 levels by Realtime quantitative PCR (RT-PCR) in patients' muscles, and MCP-1, TNF-alpha, IL-6, and Nrf2, HO-1, NQO-1 levels by RT-PCR and Western blot in EAM rats' muscles. EAM macrophages were separated, and Nrf2 over-expression macrophages were constructed. ROS level and cell migration were detected by flow cytometer and transwell assay respectively. Then, levels of MCP-1, TNF-alpha, IL-6, Nrf2, Heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO-1) were detected by RT-PCR and Western blot. RESULTS: Results showed that EAM rats were histopathologically inflammatory cell infiltration. Levels of CD163, serum CK and ROS, serum/muscle MCP-1, TNF-alpha and IL-6 increased and muscle Nrf2 level decreased in IIM patients and EAM rats. Cell migration ability and levels of ROS, MCP-1, TNF-alpha, IL-6, and plasma Nrf2 were down-regulated, and total/nucleus Nrf2, HO-1, NQO-1 were up-regulated notably when Nrf2 over-expressed. CONCLUSION: Nrf2 inhibited EAM macrophage infiltration by activating Nrf2/ARE pathway which could induce ROS degradation and inhibit pro-inflammatory factors expression. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Liu, Yutao AU - Liu Y AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China. FAU - Gao, Yuan AU - Gao Y AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China. FAU - Yang, Jing AU - Yang J AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China. FAU - Shi, Changhe AU - Shi C AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China. FAU - Wang, Yanlin AU - Wang Y AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China. FAU - Xu, Yuming AU - Xu Y AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: xuyuming@zzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181202 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Cytokines) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, rat) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (NQO1 protein, rat) SB - IM MH - Adult MH - Animals MH - Cell Movement/*immunology MH - Cytokines/immunology MH - Female MH - Gene Expression Regulation/immunology MH - Heme Oxygenase (Decyclizing)/immunology MH - Humans MH - Macrophages, Peritoneal/*immunology/pathology MH - Male MH - Middle Aged MH - NAD(P)H Dehydrogenase (Quinone)/immunology MH - NF-E2-Related Factor 2/*immunology MH - Nervous System Autoimmune Disease, Experimental/*immunology/pathology MH - Rats MH - Rats, Wistar MH - Signal Transduction/*immunology OTO - NOTNLM OT - Autoimmune myositis OT - IIM OT - Inflammatory infiltration OT - Macrophage OT - Nrf2/ARE pathway OT - PM/DM EDAT- 2018/12/05 06:00 MHDA- 2019/05/01 06:00 CRDT- 2018/12/05 06:00 PHST- 2018/07/17 00:00 [received] PHST- 2018/11/01 00:00 [revised] PHST- 2018/11/20 00:00 [accepted] PHST- 2018/12/05 06:00 [pubmed] PHST- 2019/05/01 06:00 [medline] PHST- 2018/12/05 06:00 [entrez] AID - S0161-5890(18)30578-9 [pii] AID - 10.1016/j.molimm.2018.11.014 [doi] PST - ppublish SO - Mol Immunol. 2019 Jan;105:165-172. doi: 10.1016/j.molimm.2018.11.014. Epub 2018 Dec 2.