PMID- 30142537 OWN - NLM STAT- MEDLINE DCOM- 20181224 LR - 20181224 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 107 DP - 2018 Nov TI - Orexin A may suppress inflammatory response in fibroblast-like synoviocytes. PG - 763-768 LID - S0753-3322(18)32741-0 [pii] LID - 10.1016/j.biopha.2018.07.159 [doi] AB - Orexins are peptides found in the hypothalamus and other peripheral tissues including adipose tissue, the endocrine cells of the gut, adrenal gland testis, and the pancreas. They play important roles in neuro-protection by inhibiting oxidative stress and inflammatory response via their type 1 and 2 receptors (OX1R and OX2R). The expressions of OX1R and OX2R were detected and the physiological function of orexin A in fibroblast-like synoviocytes (FLSs) was investigated in this study. Only OX1R was found on FLSs and the expression of OX1R was decreased in fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLSs) and tumor necrosis factor-alpha (TNF-alpha)-treated FLSs. Orexin A exhibited an anti-inflammatory effect on TNF-alpha treated FLSs. Particularly, orexin A treatment reduced the secretions of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) as well as the production of reactive oxygen species (ROS). Importantly, we showed that orexin A ameliorated the expression of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13). Mechanistically, we found that orexin A inhibited TNF-alpha-induced activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. The current study provides a basis for the potential application of orexin A in the clinical treatment of RA. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Sun, Minghui AU - Sun M AD - Department of Joint Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China. FAU - Wang, Weijun AU - Wang W AD - Department of Joint Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China. FAU - Li, Qing AU - Li Q AD - Department of Clinical Medicine of Chinese and Western Medicine Integration, Nanjing University of Chinese Medicine, Nanjing, 210023, China. FAU - Yuan, Tao AU - Yuan T AD - Department of Joint Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China. FAU - Weng, Wenjie AU - Weng W AD - Department of Joint Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China. Electronic address: drwengwenjie@hotmail.com. LA - eng PT - Journal Article DEP - 20180821 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (I-kappa B Proteins) RN - 0 (Interleukins) RN - 0 (NF-kappa B) RN - 0 (Orexin Receptors) RN - 0 (Orexins) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.13.12.- (Luciferases) RN - EC 3.4.24.- (MMP13 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Arthritis, Rheumatoid/pathology MH - Cell Nucleus/drug effects/metabolism MH - Fibroblasts/drug effects/metabolism/*pathology MH - Humans MH - I-kappa B Proteins/metabolism MH - Inflammation/metabolism/*pathology MH - Interleukins/metabolism MH - Luciferases/metabolism MH - Matrix Metalloproteinase 13/metabolism MH - Matrix Metalloproteinase 3/metabolism MH - NF-kappa B/metabolism MH - Orexin Receptors/metabolism MH - Orexins/*pharmacology MH - Phosphorylation/drug effects MH - Proteolysis/drug effects MH - Reactive Oxygen Species/metabolism MH - Synoviocytes/drug effects/metabolism/*pathology MH - Tumor Necrosis Factor-alpha OTO - NOTNLM OT - Fibroblast-like synoviocytes OT - Orexin A OT - Rheumatoid arthritis OT - TNF-alpha EDAT- 2018/08/25 06:00 MHDA- 2018/12/26 06:00 CRDT- 2018/08/25 06:00 PHST- 2018/04/24 00:00 [received] PHST- 2018/07/18 00:00 [revised] PHST- 2018/07/31 00:00 [accepted] PHST- 2018/08/25 06:00 [pubmed] PHST- 2018/12/26 06:00 [medline] PHST- 2018/08/25 06:00 [entrez] AID - S0753-3322(18)32741-0 [pii] AID - 10.1016/j.biopha.2018.07.159 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Nov;107:763-768. doi: 10.1016/j.biopha.2018.07.159. Epub 2018 Aug 21.