Voltage gated sodium channel 1.7 may be involved in activation monocytes of patients with Sjögren’s syndrome through BAFF signaling pathways 2328

Abstract Description Background & Purpose: We reported that the expression of a BAFF receptor, BR3, was enhanced in peripheral monocytes of patients with Sjögren’s syndrome (SS), and BAFF induced robust IL-6 production by SS monocytes as compared with healthy controls (HC). Since it is known that signal transduction pathways via voltage gated sodium channel 1.7 (Nav1.7) are involved in production of IL-6 in monocytic lineage of patients of inflammatory diseases, we investigate the possible involvement of Nav1.7 in activation of SS monocytes. Methods The expression level of Nav1.7 in peripheral monocytes from patients with SS (n = 114) and HC (n = 28) was analyzed by FACS. Peripheral monocytes were stimulated with BAFF with/without a Nav1.7 specific inhibitor. The amounts of IL-6 in the culture supernatants were measured by ELISA. The Nav 1.7 expression level in BAFF-stimulated cells was analyzed by qPCR. Results The expression level of Nav1.7 and BR3 in SS monocytes were significantly higher than those in HC. In addition, qPCR analysis indicated that BAFF enhanced the expression level of Nav1.7 in SS monocytes. The Nav1.7 expression level was significantly and positively correlated with the BR3 expression level in SS monocytes, while no such correlation was observed in HC. A Nav1.7 specific inhibitor suppressed the IL-6 production by BAFF-stimulated monocytes in a dose dependent manner. Conclusion Our data collectively suggest that Nav1,7 is involved in the BAFF-signaling pathway in SS monocytes. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)