Elevated expression levels of the voltage-gated sodium channel 1.7 and BAFF receptor in peripheral monocytes contribute to activation of monocytes of patients with primary Sjögren’s syndrome
The Journal of Immunology(2019)
Abstract
Abstract Background & Purpose We reported that elevated expression of BAFF-receptor (BR3) in peripheral monocytes of patients with primary Sjögren’s syndrome (pSS) resulted in robust increased in IL-6 production by the cells. It has been reported that the pathways via voltage-gated sodium channels, such as Nav1.7, in monocytic lineage are involved in production of inflammatory cytokines, such as IL-6, in inflammatory pain diseases. In this study, we investigated the expression levels of Nav1.7 and BR3 in peripheral monocytes in patients with pSS in an attempt to discriminate the disease from other autoimmune diseases, such as active RA and active SLE. Methods The expression levels of Nav1.7 and BR3 in peripheral monocytes were analyzed by FACS using whole blood samples from patients with pSS (n = 28), active RA (n = 15), active SLE (n = 37) and healthy controls (HC; n = 15). Peripheral monocytes were stimulated with BAFF in the presence or absence of an inhibitor against Nav1.7. The amount of IL-6 in the culture supernatants was measured by ELISA. Results FACS analysis revealed that the expression levels of Nav1.7 and BR3 in pSS monocytes was significantly higher than those of active RA (p = 0.005, 0.003), active SLE (p <0.001, 0.004) and HC (p < 0.001, 0.002). Interestingly, the expression level of Nav 1.7 in pSS monocytes was significantly and positively correlated with that of BR3 in the cells (p = 0.01). Moreover, a specific inhibitor against Nav 1.7 suppressed IL-6 production by sBAFF-stimulated peripheral monocytes in a dose dependent manner. Conclusion Our results strongly suggest that the crosstalk between BAFF signaling and sodium channel is involved in activation of pSS monocytes and can be a therapeutic target for pSS.
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