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3858490 
Journal Article 
Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells 
Zhou, X; Dong, T; Fan, Z; Peng, Y; Zhou, R; Wang, X; Song, N; Han, M; Fan, B; Jia, J; Liu, S 
2017 
Yes 
Scientific Reports
EISSN: 2045-2322 
45468 
English 
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-1β 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-1β 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 NFκB reporter provided additional evidence that these genes were involved in PFDA-induced inflammasome assembly. Furthermore, increased secretion of IL-1β 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. 
IRIS
• SR Automation
• ^Per- and Polyfluoroalkyl Substances (PFAS)
     PFOA (335-67-1) and PFOS (1763-23-1)
          Literature Search – Adverse outcome pathway (2015-present)
               WOS
     PFDA (335-76-2)
          Literature Search
               Pubmed
               WOS
• PFDA
     Literature Search
          Pubmed
          WOS
     Screening Results
          In vitro/ex vivo/in silico
               Immunotox mech
     Title and Abstract Screening
          Full Text Screening
               Studies Considered Further
                    Animal health effect studies
          Tagged as Supplemental
               Mechanistic or MOA
• PFNA
     Literature Search
          Pubmed
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          WOS
     Screening Results
          In vivo animal studies
               Immunotox
          In vitro/ex vivo/in silico
               Immunotox mech
     Literature Search Update (2013-2019)
          WOS