title: MiR-146a Regulates Inflammatory Infiltration by Macrophages in Polymyositis/Dermatomyositis by Targeting TRAF6 and Affecting IL-17/ICAM-1 Pathway.
abstract: OBJECTIVE
  The primary objective of this study was to investigate the role of miR-146a in inducing the inflammatory infiltration of macrophages in polymyositis/dermatomyositis (PM/DM) through targeting TNF receptor associated factor 6 (TRAF6), which may further down-regulate the Interleukin-17 (IL-17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway.
  
  
  METHODS
  Biopsies were collected from PM/DM patients and healthy volunteers. PM/DM model establishment and macrophage isolation were performed on Sprague Dawley (SD) rats. Model rats and macrophages were treated with anti-IL-17, anti-ICAM-1, miR-146a mimics, miR-146a inhibitors, and TRAF6 siRNAs. Serum creatine phosphokinase (S-CK) expression was assessed using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry assay was performed to analyze CD163 expression in muscle samples. Furthermore, we used transwell assay to test cell migration; RT-PCR and western blot were carried out to determine the expression of miR-146a, TRAF6, IL-17, and ICAM-1.
  
  
  RESULTS
  The S-CK, TRAF6, IL-17 and ICAM-1 levels were higher in PM/DM patients compared with healthy controls and were down-regulated after the conventional treatment. Treatment with miR-146a mimics, anti-IL-17 and anti-ICAM-1 decreased the expression of IL-17 and ICAM-1, whereas miR-146a inhibitors exerted the opposite effects. The effects of miR-146a inhibitors were suppressed by treatment with TRAF6 siRNA. In addition, the luciferase reporter assay validated the targeting relationship between miR-146a and TRAF6.
  
  
  CONCLUSIONS
  MiR-146a regulates inflammatory macrophage infiltration in PM/DM by targeting TRAF6 and affecting the IL-17/ICAM-1 pathway.
authors.affiliation: Cancer Institute, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Yuanqin
authors.initials: Y
authors.lastname: Yin
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Songlin
authors.initials: S
authors.lastname: Li
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cai
authors.forename: Youhong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001483:Base Sequence; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000097:blood; D003882:Dermatomyositis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006728:Hormones; D020381:Interleukin-17; C542542:MIRN146 microRNA, human; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D011956:Receptors, Cell Surface; D048029:TNF Receptor-Associated Factor 6; D018799:Intercellular Adhesion Molecule-1; D003402:Creatine Kinase