Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells

Abstract

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.

Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence

“…In the present study, we discovered the key role of cIAP2 in this process. cIAP2 not only played an important role in the secretion of interleukin as previously reported (55), but also downregulated the expression of p53. p53 is an important molecule that regulates cell apoptosis and the cell cycle, however apoptosis and the cell cycle did not exhibit the expected results after PFDA treatment and this may be related to downregulation of p53 and its downstream molecules.…”

Risk to human health related to the presence of perfluoroalkyl substances in food

“…Both these studies by Fang et al (2008Fang et al ( , 2009 and by Zhou et al (2017) do therefore indicate that components of the immune system are affected by PFNA and PFDA. Whether such effects of PDFA would have an impact on the functionality of the immune system, including antibody production, has not been studied.…”

“…In an in vitro study performed by Zhou et al (2017), the human gastric cell line AGS was exposed to PFDA, and increased IL-13 and IL-18 expression, both at the protein level and the mRNA level, were observed. Also NLRP3 and NF-jB were increased, indicating enhanced inflammasome activity.…”

Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity

“…The NLRP3 inflammasome has been implicated in the pathogenesis of MS and EAE (Barclay and Shinohara, 2017) via both T cell-extrinsic (Li et al, 2019) and T cell-intrinsic (Martin et al, 2016) processes. We noted that several ex-Th17 transcripts that were upregulated in male cells-Il18r1, Cxcr6, and Relencode either upstream regulators or downstream targets of inflammasome signaling (Inoue et al, 2012;Prencipe et al, 2014;Zhou et al, 2017). It was recently shown that the caspase-1 and inflammasome inhibitor VX-765 reduced IL-18 secretion and improved behavioral outcomes in the acute C57BL/6J model of EAE (McKenzie et al, 2018).…”