Up-regulated signaling pathway triggered by sBAFF may induce aberrant production of IL-6 in monocytes of the patients with Sjögren’s Syndrome (34.16)

Abstract

Abstract Background and Purpose: Elevated production of BAFF seemed to be involved in the development of autoimmune diseases such as Sjögren’s syndrome (SS). We have demonstrated 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 analyzed by ELISA and/or semi-quantitative RT-PCR. Results and Discussion: IFN-gamma induced the production of sBAFF and IL-6 in SS monocytes. The production of IL-6 in SS monocytes was significantly suppressed by an anti-BAFF antibody or rBAFF receptor. In addition, stimulation of SS monocytes with sBAFF induced robust increase in the production of IL-6. Moreover, expression of BAFF receptor was also enhanced in SS monocytes upon stimulation. 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, such as NF-kB2 and NF-IL-6, were aberrantly elevated in SS monocytes. These data strongly suggest that sBAFF produced in monocytes activates the expression of IL-6, and that signal transduction triggered by sBAFF may be impaired in SS monocytes.