The P2X(7) receptor-pannexin connection to dye uptake and IL-1beta release.-猫眼课题宝

P2X（7）受体 - 铅内蛋白与染料摄取和IL-1Beta释放的连接。

DOI：

10.1007/s11302-009-9141-7

发表时间：

2009-06

期刊：

PURINERGIC SIGNALLING

影响因子：

3.5

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

Pelegrin, Pablo;Surprenant, Annmarie

关键词：

Caspase-1 Inflammasome Dye uptake Inflammation Macrophage

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686830/?report=classic

P2X7受体(P2X7R)独特地与两种不同的细胞反应有关：激活一条染料通透途径，允许分子通过长达900kDa的分子，以及从激活的巨噬细胞快速释放促炎细胞因子IL-1β(IL-1β)。这种染料摄取途径是如何形成的，以及它是否参与了IL-1β的释放，目前尚不清楚。PAnnexin-1是最近发现的一种与P2X7R物理上相关的蛋白质。抑制pAnnexin-1不会改变P2X7R离子通道的激活或相关的钙通量，但会阻断P2X7R诱导的染料摄取的一个成分，并揭示一条以前未发现的较慢的染料摄取途径。抑制pAnnexin-1可阻断P2X7R介导的巨噬细胞IL-1β的释放，也可阻断其他与CAPase-1激活相关的刺激物介导的释放，还可抑制IL-1家族成员IL-1α的释放，而IL-1家族的处理不需要caspase-1的激活。因此，PAnnexin-1与染料摄取和IL-1β释放有关，但通过不同的机制。

The P2X7 receptor (P2X7R) is uniquely associated with two distinct cellular responses: activation of a dye-permeable pathway allowing passage of molecules up to 900 Da and rapid release of the pro-inflammatory cytokine, interleukin-1β (IL-1β), from activated macrophage. How this dye uptake path forms and whether it is involved in IL-1β release has not been known. Pannexin-1 is a recently identified protein found to physically associate with the P2X7R. Inhibition of pannexin-1 does not alter P2X7R ion channel activation or associated calcium flux but blocks one component of P2X7R-induced dye uptake and unmasks a slower, previously undetected, dye uptake pathway. Inhibition of pannexin-1 blocks P2X7R-mediated IL-1β release from macrophage as well as release mediated by other stimuli which couple to activation of capase-1 and additionally inhibits the release of interleukin-1α, a member of the IL-1 family whose processing does not require caspase-1 activation. Thus, pannexin-1 is linked to both dye uptake and IL-1β release but via distinct mechanisms.