Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells

作者

Zhou, XY;Dong, TY;Fan, ZY;Peng, YP;Zhou, RB;Wang, XQ;Song, N;Han, MY;Fan, BB;Jia, JH;Liu, SL

作者单位

[Zhou, Xiangyu; Peng, Yanping; Song, Ning; Jia, Jihui; Liu, Shili] Shandong Univ, Sch Basic Med Sci, Dept Med Microbiol, Jinan 250012, Shandong, Peoples R China.;-;[Dong, Tianyi; Han, Mingyong] Shandong Univ, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China.;-;[Fan, Ziyan] China Natl Tobacco Qual Supervis & Test Ctr, 2 Fengyang St, Zhengzhou, Henan, Peoples R China.;-;[Zhou, Rongbin; Wang, Xiaqiong] Univ Sci & Technol China, Sch Life Sci & Med Ctr, Inst Immunol, Hefei 230027, Anhui, Peoples R China.;-;[Zhou, Rongbin; Wang, Xiaqiong] Univ Sci & Technol China, Sch Life Sci & Med Ctr, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Anhui, Peoples R China.;-;[Fan, Bingbing] Shandong Univ, Sch Publ Hlth, Jinan 250012, Shandong, Peoples R China.

摘要

Perfluorodecanoic acid (PFDA), a perfluorinated carboxylic acid, presents in the environment and accumulates in human blood and organs, but its association with tumor promotion are not clear. Given that inflammation plays a significant role in the development of gastric malignancies, we evaluated the effects of PFDA on activation of the inflammasome and inflammation regulation in the gastric cell line AGS. When added to cell cultures, PFDA significantly stimulated IL-1 beta and IL18 secretion and their mRNA levels compared with control cells. By RT-PCR and western-blot we found that up-regulation of NLRP3 were associated with promotion of IL-1 beta and IL-18 production. Then expression variation of cIAP1/ 2, c-Rel and p52 were analyzed, the results demonstrated raised mRNA expression in all the tested genes concomitant with enhanced inflammasome activity after exposure to PFDA. Assays with cIAP2 siRNA and NF kappa B reporter provided additional evidence that these genes were involved in PFDA-induced inflammasome assembly. Furthermore, increased secretion of IL-1 beta and IL-18 were detected in stomach of PFDA-treated mice, disorganized alignment of epithelial cells and inflammatory cell infiltration were also observed in the stomach tissues upon PFDA treatment. This study reports for the first time that PFDA regulates inflammasome assembly in human cells and mice tissues.

关键词

ALPHA-DEPENDENT APOPTOSIS; KAPPA-B ACTIVATION; NEW-YORK-STATE; PERFLUOROOCTANESULFONATE PFOS; PERFLUORINATED COMPOUNDS; SERUM CONCENTRATIONS; BLOOD-DONORS; CANCER; EXPOSURE; INHIBITOR

基本信息

所属机构:

归属医师: 韩明勇董天一

PMID：28367997

UT：000398108500001

刊名:SCIENTIFIC REPORTS

年，卷(期):2017年7卷

DOI：10.1038/srep45468

附件： pdf

收录: SCIE