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.

• Authors: Xiangyu Zhou, Tianyi Dong, Ziyan Fan, Yanping Peng, Rongbin Zhou, Xiaqiong Wang, Ning Song, Mingyong Han, Bingbing Fan, Jihui Jia, Shili Liu
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 45468 (04 03 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28367997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Decanoic Acids
• Fluorocarbons
• Inflammasomes
• Interleukin-18
• Interleukin-1beta
• NF-kappa B p52 Subunit
• NLR Family, Pyrin Domain-Containing 3 Protein
• RNA, Small Interfering
• Transcription Factor RelA
• perfluorodecanoic acid
• BIRC3 protein, human
• Baculoviral IAP Repeat-Containing 3 Protein
• Caspase 1

Topics

• Animals
• Baculoviral IAP Repeat-Containing 3 Protein (antagonists & inhibitors, genetics, metabolism)
• Caspase 1 (metabolism)
• Cell Line, Tumor
• Decanoic Acids (pharmacology)
• Fluorocarbons (pharmacology)
• Gastric Mucosa (cytology, drug effects, metabolism)
• Humans
• Inflammasomes (drug effects, metabolism)
• Interleukin-18 (analysis, genetics, metabolism)
• Interleukin-1beta (analysis, genetics, metabolism)
• Mice
• NF-kappa B p52 Subunit (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Stomach (drug effects, pathology)
• Transcription Factor RelA (metabolism)