(The FASEB Journal. 2008;22:664.6)
© 2008 FASEB
(The FASEB Journal. 2008;22:664.6.)
© 2008 FASEB
Impaired regulation of BAFF production in monocytes of patients with Sjögren's syndrome
Keiko Yoshimoto,
Maiko Tanaka,
Yumiko Setoyama,
Katsuya Suzuki,
Kensei Tsuzaka,
Tohru Abe and
Tsutomu Takeuchi
Div of Rheumatology and Clinical Immunology, Saitama Medical University, Kawagoe, Japan
ABSTRACT
B cell activating factor belonging to the TNF family (BAFF) is mainly expressed in monocytes and dendritic cells and regulates proliferation, differentiation, and survival of B cells. Accumulating evidence suggests that BAFF plays a pivotal role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS). Therefore, elucidation of the mechanism of BAFF production is important not only to understand the mechanism of pathogenesis of the autoimmune diseases, but also to explore therapeutic possibilities to treat the diseases. In this study, we analyzed the expression of cytokines in peripheral monocytes prepared from SS patients and found that the expression of BAFF was abnormally enhanced upon stimulation with IFN-gamma, an inducer of IgG, as compared with normal monocytes. IFN-gamma also induced robust production of BAFF in a human mononuclear cell line, THP-1, and morphological change of the cells, indicating that a signal transduction pathway triggered by IFN-gamma is involved in the expression of BAFF in mononuclear cells. Simultaneous induction of the expression of IL-6, TNF-alpha and IP-10 was observed in both SS monocytes and THP-1 upon stimulation. These results suggest that SS monocytes and THP-1 share a common mechanism of production of BAFF and hence THP-1 provides a useful model to investigate the abnormal production of BAFF in SS monocytes.
