IL-1RA is part of the inflammasome-regulated immune response in bladder epithelial cells and influences colonization of uropathogenic E. coli
IL-1RA is part of the inflammasome-regulated immune response in bladder epithelial cells and influences colonization of uropathogenic E. coli
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DOI：
10.1016/j.cyto.2019.154772
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发表时间：
2019-11-01
期刊：
影响因子：
3.8
通讯作者：
Demirel, Isak
中科院分区：
文献类型：
--
作者：
Lindblad, Anna;Persson, Katarina;Demirel, Isak
最近已经提出NLRP 3炎性体、IL-1 β释放和焦亡（细胞裂解）对于尿路感染（UTI）的进展和细胞内细菌小生境的消除是必不可少的。然而，IL-1 R拮抗剂（IL-1 RA）在UTI期间对免疫应答的影响，除了其破坏IL-1 β信号传导的能力之外，还没有得到很好的理解。本研究的目的是探讨IL-1 RA在膀胱上皮细胞UPEC定植和随后的宿主炎症反应中的作用。用UPEC分离物CFT 073刺激人膀胱上皮细胞（5637）和CRISPR/Cas9产生的NLRP 3和半胱天冬酶-1敲低细胞和IL-1 RA敲除细胞。结果表明，UPEC毒力因子α-溶血素是IL-1 RA释放所必需的，并且炎性小体相关蛋白caspase-1和NLRP 3影响IL-1 RA的释放。与野生型细胞相比，IL-1 RA缺陷型细胞显示CFT 073的粘附和侵袭降低，表明IL-1 RA可能对抗保护免受细菌定植的机制。炎症相关蛋白的靶向蛋白质分析显示，与Cas9对照细胞相比，在IL-1 RA缺陷型膀胱上皮细胞中，23种蛋白质的基础表达和10种蛋白质的UPEC诱导的表达显著改变。这表明IL-1 RA对膀胱上皮细胞中的炎症反应具有广泛的影响。
The NLRP3 inflammasome, IL-1 beta release and pyroptosis (cell lysis) have recently been proposed to be essential for the progression of urinary tract infection (UTI) and elimination of intracellular bacterial niches. However, the effects of IL-1R antagonist (IL-1RA) on immune responses during UTI, except for its ability to disrupt IL-1 beta signalling, are not well understood. The aim of this study was to investigate the role of IL-1RA in UPEC colonization of bladder epithelial cells and the subsequent host inflammatory response. Human bladder epithelial cells (5637) and CRISPR/Cas9 generated NLRP3 and caspase-1 knockdown cells and IL-1RA knockout cells were stimulated with the UPEC isolate CFT073. The results showed that the UPEC virulence factor alpha-hemolysin is essential for IL-1RA release, and that the inflammasome-associated proteins caspase-1 and NLRP3 affect the release of IL-1RA. IL-1RA deficient cells showed a reduced adherence and invasion by CFT073 compared to wild-type cells, suggesting that IL-1RA may oppose mechanisms that protects against bacterial colonization. A targeted protein analysis of inflammation-related proteins showed that the basal expression of 23 proteins and the UPEC-induced expression of 10 proteins were significantly altered in IL-1RA deficient bladder epithelial cells compared to Cas9 control cells. This suggests that IL-1RA has a broad effect on the inflammatory response in bladder epithelial cells.