title: Increased Syk phosphorylation leads to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown.
  
  
  METHODS
  Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients.
  
  
  RESULTS
  Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-naïve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression.
  
  
  CONCLUSIONS
  Our results suggest that the activated Syk-mediated TRAF6 pathway leads to aberrant activation of B cells in SLE, and also highlight Syk as a potential target for B-cell-mediated processes in SLE.
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iwata
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Niiro
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Jabbarzadeh-Tabrizi
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: S-P
authors.initials: SP
authors.lastname: Wang
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akashi
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan tanaka@med.uoeh-u.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D000072377:Syk Kinase; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000276:immunology; D055815:Young Adult
chemical_list: C477642:2-(7-(3,4-dimethoxyphenyl)imidazo(1,2-c)pyrimidin-5-ylamino)nicotinamide; D018941:Antigens, CD19; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011743:Pyrimidines; C120635:TAX1BP1 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D009536:Niacinamide; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase
keywords: B cell; Syk; Systemic lupus erythematosus; TRAF6; neuropsychiatric lupus; renal lupus