Alarmin HNP-1 promotes pyroptosis and IL-1β release through different roles of NLRP3 inflammasome via P2X7 in LPS-primed macrophages:

Innate Immunity

QixingChen¹ 

关键词: Defensin;    immunomodulation;    pyroptosis;    cytokine;    signal transduction;   

DOI  :  10.1177/1753425913490575

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Defensins are the first endogenous mediators to be characterized as alarmins and play multifunctional roles in immune response. Previous studies reported that human neutrophil peptide (HNP)-1, a member of the α-defensin subfamily, could regulate the IL-1β post-translational process; however, the underlying mechanism remained unknown. Using an LPS-primed THP-1 macrophage model, we found that inhibition of P2X purinoceptor 7 (P2X7) suppressed HNP-1-initiated mature IL-1β release. Confocal microscopy and glutathione S-transferase (GST) pull-down assay demonstrated that HNP-1 bound to P2X7 directly. HNP-1 treatment increased the activated level of caspase-1, and inhibition of caspase-1 abolished IL-1β release. Incubation of LPS-primed macrophages with potassium chloride also prevented HNP-1-induced export of mature IL-1β. Likewise, an ethidium bromide uptake test showed that the P2X7-K+ efflux-caspase-1 signaling pathway triggered by HNP-1 contributed to pyroptotic pore formation. Furthermore, knock down of i...

【 授权许可】

CC BY