title: MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis.
abstract: To test the hypothesis that miR-155 regulates monocyte migratory potential via modulation of chemokine and chemokine receptor expression in RA, and thereby is associated with disease activity.
  
  
  
  The miR-155 copy-numbers in monocytes from peripheral blood (PB) of healthy (n = 22), RA (n = 24) and RA SF (n = 11) were assessed by real time-PCR using synthetic miR-155 as a quantitative standard. To evaluate the functional impact of miR-155, human monocytes were transfected with control or miR-155 mimic, and the effect on transcript levels, and production of chemokines was evaluated by Taqman low-density arrays and multiplex assays. A comparative study evaluated constitutive chemokine receptor expression in miR-155-/-and wild-type murine (CD115+Ly6C+Ly6G-) monocytes.
  
  
  
  Compared with healthy monocytes, the miR-155 copy-number was higher in RA, peripheral blood (PB) and SF monocytes (PB P < 0.01, and SF P < 0.0001). The miR-155 copy-number in RA PB monocytes was higher in ACPA-positive compared with ACPA-negative patients (P = 0.033) and correlated (95% CI) with DAS28 (ESR), R = 0.728 (0.460, 0.874), and with tender, R = 0.631 (0.306, 0.824) and swollen, R = 0.503 (0.125, 0.753) joint counts. Enforced-expression of miR-155 in RA monocytes stimulated the production of CCL3, CCL4, CCL5 and CCL8; upregulated CCR7 expression; and downregulated CCR2. Conversely, miR155-/-monocytes showed downregulated CCR7 and upregulated CCR2 expression.
  
  
  
  Given the observed correlations with disease activity, these data provide strong evidence that miR-155 can contribute to RA pathogenesis by regulating chemokine production and pro-inflammatory chemokine receptor expression, thereby promoting inflammatory cell recruitment and retention in the RA synovium.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.|Benghazi Medical Center, Medical School, Benghazi University, Benghazi, Libya.
authors.forename: Aziza
authors.initials: A
authors.lastname: Elmesmari
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.|Development and Innovation, Scottish National Blood Transfusion Service, Research, Edinburgh, UK.
authors.forename: Alasdair R
authors.initials: AR
authors.lastname: Fraser
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Wood
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Gilchrist
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Vaughan
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: Stewart
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK mariola.kurowska-stolarska@glasgow.ac.uk.
authors.forename: Mariola
authors.initials: M
authors.lastname: Kurowska-Stolarska
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D019707:Receptors, Chemokine
keywords: chemokines; disease activity; microRNA-155; monocyte; rheumatoid arthritis