Clinical neurology and neurosurgery · 2017
Increased expression of P2X7 receptor in peripheral blood mononuclear cells correlates with clinical severity and serum levels of Th17-related cytokines in patients with myasthenia gravis.
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Zhang Yong, Zhang Yanyan, Li Hao, Jia Xiao, Zhang Xiuying, Xia Yan, Wang YuZhong, Fu Linlin, Xiao Chenghua, Geng Deqin
Аннотация
OBJECTIVES: P2X7R is a well-documented activator of innate and adaptive immune responses. We aimed to measure the expression levels of P2X7R in peripheral blood mononuclear cells (PBMCs) from patients with myasthenia gravis (MG) and to investigate whether the expression of P2X7R is associated with pathogenesis of MG.
PATIENTS AND METHODS: A total of 32 patients with MG (12 generalized MG (GMG) and 20 Ocular MG (OMG) and 22 healthy donors were recruited in this study. The quantitative MG score was used to evaluate the clinical severity. Real-time PCR and western blot were used to measure the levels of P2X7R expressed in PBMCs. Serum Th17-related cytokines (IL-1β, IL-6, IL-17 and IL-21) were tested by ELISA. PBMCs from MG patients were purified and challenged by LPS with or without a selective P2X7R inhibitor (BBG).
RESULTS: Our results showed that the expression of P2X7R mRNA and protein in PBMCs was increased in MG patients compared with healthy controls, with higher expression in generalized patients (GMG) than in ocular patients (OMG). In addition, P2X7R expression presents a significantly positive correlation with clinical severity and serum levels of IL-1β, IL-6, IL-17 and IL-21 in MG. In cultured MG PBMC, LPS challenge led to up-regulated P2X7R expression accompanied with increased production of IL-1β, IL-6, IL-17 and IL-21. Importantly, P2X7R blockade with BBG significantly attenuates the LPS-induced production of cytokines.
CONCLUSION: P2X7R expression was up-regulated in MG and LPS-P2X7R axis may be involved in the pathogenesis of MG by promoting Th17 immune response.
PATIENTS AND METHODS: A total of 32 patients with MG (12 generalized MG (GMG) and 20 Ocular MG (OMG) and 22 healthy donors were recruited in this study. The quantitative MG score was used to evaluate the clinical severity. Real-time PCR and western blot were used to measure the levels of P2X7R expressed in PBMCs. Serum Th17-related cytokines (IL-1β, IL-6, IL-17 and IL-21) were tested by ELISA. PBMCs from MG patients were purified and challenged by LPS with or without a selective P2X7R inhibitor (BBG).
RESULTS: Our results showed that the expression of P2X7R mRNA and protein in PBMCs was increased in MG patients compared with healthy controls, with higher expression in generalized patients (GMG) than in ocular patients (OMG). In addition, P2X7R expression presents a significantly positive correlation with clinical severity and serum levels of IL-1β, IL-6, IL-17 and IL-21 in MG. In cultured MG PBMC, LPS challenge led to up-regulated P2X7R expression accompanied with increased production of IL-1β, IL-6, IL-17 and IL-21. Importantly, P2X7R blockade with BBG significantly attenuates the LPS-induced production of cytokines.
CONCLUSION: P2X7R expression was up-regulated in MG and LPS-P2X7R axis may be involved in the pathogenesis of MG by promoting Th17 immune response.