Research Associate Keio University School of Medicine Tokyo, Japan
Disclosure(s):
Keiko Yoshimoto: No financial relationships to disclose
Introduction/Rationale: We reported that the expression of a BAFF receptor, BR3, was enhanced in monocytes in patients with Sjögren’s disease (SjD), and that BAFF induced production of IL-6 by the cells. In addition, we found that IL-6 produced by BAFF-stimulated monocyte induced IgG production by co-cultured B cells. In our previous study, we also found that the inhibitors against Nav channel suppressed BAFF-induced IL-6 production by THP-1, a human monocytic leukemia cell line. Since the voltage gated sodium channel 1.7 (Nav1.7) was known to be involved in the production of IL-6 in monocytic lineage of patients of inflammatory diseases, we investigated the possible involvement of Nav1.7 in the BAFF signaling pathway in SjD monocytes.
Methods: The expression levels of BR3 and Nav1.7 in peripheral monocytes from patients with SjD (n = 108) and healthy controls (HC; n = 28) were analyzed by FACS. PBMCs were stimulated in vitro with a mixture of anti-IgM, anti-CD40, IL-21 and BAFF in the presence or absence of a specific inhibitor against Nav1.7. The amount of IgG produced by the cells was measured by ELISA. The expression level of Nav1.7 in the cells was analyzed by qPCR.
Results: The proportion of Nav1.7- and BR3-positive cells in monocytic population (Nav1.7+/CD14+, BR3+/CD14+) were significantly elevated in SjD as compared to HC. The Nav1.7+/CD14+ ratio was significantly correlated with BR3+/CD14+ ratio in SjD patients. Of note is that BAFF induced not only IL-6 production by SjD monocytes, but also the Nav1.7 expression in the cells. Moreover, a Nav1.7 specific inhibitor suppressed BAFF-induced IL-6 overproduction by SjD monocytes and elevated IgG production from stimulated PBMCs in a dose dependent manner.
Conclusion: These data and our previous data collectively suggest that Nav 1.7 signaling pathway is involved in the BAFF signaling pathway especially in IL-6 production by monocytes and IgG production by B cells in SjD.
