NF-kB is involved in abnormal BAFF signaling in peripheral monocytes of patients with primary Sjögren’s syndrome. (P6274)

Abstract

Abstract Background and Purpose: We revealed that BAFF induced a robust increase in the production of IL-6 by monocytes from patients with primary Sjögren’s syndrome(pSS), and that the expression levels of a BAFF receptor (BR3) , NF-IL-6 and NF-kB2 were enhanced in pSS monocytes compared to the control. The purpose of this study is to elucidate the possible abnormalities of a BAFF signaling pathway in pSS monocytes. Materials and Methods: The expression level of BR3 on monocytes in whole blood from pSS patients or normal control was analyzed by FACS. Peripheral monocytes were stimulated with soluble BAFF (sBAFF), and the production of IL-6 by the cells was measured by ELISA. The expression levels of IKK-alpha and IKK-beta were analyzed by western blotting. Results and Discussion: FACS analysis showed that the expression level of BR3 was significantly elevated in pSS monocytes compared to the control. Interestingly, the expression level of BR3 on pSS monocytes was positively correlated with the amount of IL-6 produced by sBAFF-treated monocytes. Moreover, NF-kB activation inhibitor suppressed the IL-6 production by sBAFF-treated pSS monocytes in a dose-dependent manner. In addition, phosphorylation levels of IKK-alpha and IKK-beta in pSS monocytes were enhanced upon stimulation with sBAFF. These data suggest that sBAFF acts through BR3 to induce the expression of IL-6 in monocytes, and that IKK-alpha and IKK-beta are involved in the signal transduction pathway triggered by sBAFF.