Plasticizer DBP Activates NLRP3 Inflammasome through the P2X7 Receptor in HepG2 and L02 Cells

Plasticizer DBP Activates NLRP3 Inflammasome through the P2X7 Receptor in HepG2 and L02 Cells
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DOI:
10.1002/jbt.21776
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发表时间:
2016-04-01
影响因子:
3.6
通讯作者:
Wang, Nanping
Wang, Nanping
中科院分区:
医学4区
文献类型:
--
作者:
Ni, Jiahua;Zhang, Zihui;Wang, Nanping

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邻苯二甲酸二丁酯(DBP)是最广泛使用的增塑剂之一,可迁移出来污染我们的身体和环境。大量研究表明,DBP与肝脏病变和疾病密切相关。炎性小体是由蛋白酶原和模式识别受体如核苷酸寡聚化结构域(NOD)样受体家族、pyrin结构域3(NLRP 3)组成的多蛋白复合物。NLRP 3炎性体的激活参与肝损伤的发病机制。本研究的目的是确定DBP对NLRP 3炎性小体的影响。我们发现,DBP触发肝细胞系中NLRP 3炎性体的激活。用Ca-074-Me、N-乙酰半胱氨酸和KN-62观察到P2 X(7)受体参与了DBP诱导的NLRP 3炎性体的激活。DBP也可触发ATP的释放。总之,我们证明DBP是NLRP 3炎性体的激活剂之一,并可能在肝损伤中起重要作用。
Ditubyl phthalate (DBP), one of the most widely used plasticizers, can migrate out to contaminate our bodies and environment. A number of studies have showed that DBP is closely related to liver pathological changes and diseases. Inflammasomes are multiprotein complexes composed of procaspase and pattern recognition receptors such as Nucleotide oligomerization domain (NOD) like receptor family, pyrin domain containing 3 (NLRP3). Activation of NLRP3 inflammasome is implicated in the pathogeneses of liver damage. The aim of this study was to determine the effects of DBP on NLRP3 inflammasome. We found that DBP triggered the activation of NLRP3 inflammasome in hepatocyte cell lines. By using Ca-074-Me, N-acetylcysteine and KN-62, we observed that the P2X(7) receptor participated in the DBP-induced activation of NLRP3 inflammasome. DBP could also trigger the ATP release. In conclusion, we demonstrated that DBP is one of the activator of NLRP3 inflammasome and may play an important role in liver damage.