S Iwata1, K Yamaoka1, H Niiro2, S Jabbarzadeh-Tabrizi2, S-P Wang1, M Kondo1, M Yoshikawa1, K Akashi2, Y Tanaka3. 1. The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. 2. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan tanaka@med.uoeh-u.ac.jp.
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. CONCLUSION: 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.
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 SLEpatients. RESULTS: Pronounced phosphorylation and expression of Syk were noted in B cells from SLEpatients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLEpatients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLEpatients. 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. CONCLUSION: 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.
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