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.
Highlights
Gastric cancer is the second leading cause of cancer death worldwide and accounts for about 10% of all invasive cancers[1]
To assess effects of Perfluorodecanoic acid (PFDA) on the secretion of the cytokines that may be regulated by the inflammasome mechanism, we treated the gastric epithelial cell line AGS with PFDA and monitored IL-1βand IL-18 productions by enzyme-linked immunosorbent assay (ELISA)
PFDA enhanced IL-1βproduction in culture media by more than 90% compared with control cells within 24 h; this ratio increased to 220% for IL-18
Summary
Gastric cancer is the second leading cause of cancer death worldwide and accounts for about 10% of all invasive cancers[1]. The total number of cases and deaths from gastric cancer have increased concomitant with extensive demographic changes and ongoing increase of environmental pollution in China. While the pathogenesis of gastric cancer is not completely understood, epidemiological studies suggest that chronic inflammation plays a significant role in the development of gastric malignancies[11]. Some evidence suggested that NLRs are closely correlated to cancer occurrence, the level of IL-1βand IL-18 were found to be significantly elevated in various types of malignancies[12,14,15]. We found that PFDA induced IL-1βand IL-18 secretion in culture solution of cell line AGS and mice stomachs. This study reports for the first time that PFDA activates inflammasome and promotes gastric inflammation in gastric cells and mice tissues
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