Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
复制标题
DOI：
10.1038/sj.cdd.4402195
复制
发表时间：
2007-09-01
影响因子：
12.4
通讯作者：
Tschopp, J.
中科院分区：
文献类型：
--
作者：
Petrilli, V.;Papin, S.;Tschopp, J.
炎性小体是含有Nod样受体（NLR）和半胱天冬酶-1的细胞质多蛋白复合物，其在组装时加工并激活促炎细胞因子白细胞介素（IL）-1β和IL-18。携带NLR成员NALP 1、NALP 3和IPAF的炎性小体已被最好地表征。虽然IPAF炎性体被细菌鞭毛蛋白激活，但NALP 3炎性体的激活不仅由几种微生物组分触发，而且还由过多的与细菌相关的宿主分子如尿酸触发。NALP 3如何感知这些化学上不相关的激活剂尚不清楚。在这里，我们提供的证据表明，NALP 3的激活，但不是IPAF炎性体，是通过抑制K+流出细胞。低细胞内K+也是炭疽杆菌致死毒素激活NALP 1炎性小体的必要条件。在体外，当K+浓度低于90 mM时，NALP炎性体组装和半胱天冬酶-1募集自发发生，但在较高浓度下会被阻止。因此，低细胞内K+可能是NALP炎性小体激活的最不常见的触发因素。
Inflammasomes are Nod-like receptor (NLR)-and caspase-1-containing cytoplasmic multiprotein complexes, which upon their assembly, process and activate the proinflammatory cytokines interleukin (IL)-1β and IL-18. The inflammasomes harboring the NLR members NALP1, NALP3 and IPAF have been best characterized. While the IPAF inflammasome is activated by bacterial flagellin, activation of the NALP3 inflammasome is triggered not only by several microbial components, but also by a plethora of danger-associated host molecules such as uric acid. How NALP3 senses these chemically unrelated activators is not known. Here, we provide evidence that activation of NALP3, but not of the IPAF inflammasome, is blocked by inhibiting K+ efflux from cells. Low intracellular K+ is also a requirement for NALP1 inflammasome activation by lethal toxin of Bacillus anthracis. In vitro, NALP inflammasome assembly and caspase-1 recruitment occurs spontaneously at K+ concentrations below 90 m M, but is prevented at higher concentrations. Thus, low intracellular K+ may be the least common trigger of NALP-inflammasome activation.