Signaling pathway triggered by sBAFF may be impaired in monocytes of the patients with Sjögren’s Syndrome (137.43)

Abstract

Abstract Background and Purpose: B cell activating factor belonging to the TNF superfamily (BAFF) is indispensable for proliferation, differentiation and survival of B cells. Several lines of evidence suggest that elevated production of BAFF seemed to be involved in the development of autoimmune diseases such as Sjögren's syndrome (SS). In our previous study, we investigated that BAFF and IL-6 were abnormally produced in SS monocytes upon stimulation with IFN-gamma. In the present study, we investigated a regulatory mechanism of the production of these cytokines in SS monocytes. Materials and Methods: Peripheral monocytes prepared from SS patients and normal individuals were stimulated with IFN-gamma or soluble BAFF (sBAFF). The expression levels of sBAFF, IL-6 and transcription factors were measured by ELISA and/or semi-quantitative RT-PCR. Results and Discussion: IFN-gamma remarkably induced the production of sBAFF and IL-6 in SS monocytes. The production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of SS monocytes with sBAFF induced robust increase in the production of IL-6. These data suggest that the production of IL-6 in monocytes is induced partly through a signal transduction pathway triggered by sBAFF. We found that the expression levels of several transcription factors were aberrantly elevated in SS monocytes as compared with normal monocytes. These data strongly suggest that sBAFF produced in monocytes acts in an autocrine or paracrine fashion to activate the expression of the IL-6 gene, and that signal transduction triggered by sBAFF may be impaired in SS monocytes. This aberration may underlie the development of SS.