Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Eur J Immunol. 2013 May;43(5):1147-52. doi: 10.1002/eji.201243187. Epub 2013 Mar 15.
Inflammasomes are multi-protein platforms that drive the activation of caspase-1 leading to the processing and secretion of biologically active IL-1β and IL-18. Different inflammasomes including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLR caspase-recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) are activated and assembled in response to distinct microbial or endogenous stimuli. However, the mechanisms by which upstream stimuli trigger inflammasome activation remain poorly understood. Double-stranded RNA-activated protein kinase (PKR), a protein kinase activated by viral infection, has been recently shown to be required for the activation of the inflammasomes. Using macrophages from two different mouse strains deficient in PKR, we found that PKR is important for the induction of the inducible nitric oxide synthase (iNOS). However, PKR was dispensable for caspase-1 activation, processing of pro-IL-1β/IL-18 and secretion of IL-1β induced by stimuli that trigger the activation of NLRP3, NLRC4 and AIM2. These results indicate that PKR is not required for inflammasome activation in macrophages.
炎性小体是一种多蛋白平台，可驱动半胱天冬酶-1 的激活，导致生物活性 IL-1β 和 IL-18 的加工和分泌。不同的炎性小体，包括 NOD 样受体（NLR）家族富含 pyrin 域的 3（NLRP3）、NLR 半胱氨酸天冬氨酸蛋白酶募集域 4（NLRC4）和黑色素瘤缺失 2（AIM2），在响应不同的微生物或内源性刺激时被激活和组装。然而，上游刺激触发炎性小体激活的机制仍知之甚少。双链 RNA 激活蛋白激酶（PKR）是一种被病毒感染激活的蛋白激酶，最近被证明是炎性小体激活所必需的。使用两种不同的 PKR 缺陷型小鼠巨噬细胞，我们发现 PKR 对于诱导可诱导型一氧化氮合酶（iNOS）的产生是重要的。然而，PKR 对于 caspase-1 的激活、前体 IL-1β/IL-18 的加工以及由触发 NLRP3、NLRC4 和 AIM2 激活的刺激诱导的 IL-1β 的分泌是可有可无的。这些结果表明，PKR 不是巨噬细胞中炎性小体激活所必需的。
