title: 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.affiliation: Department of medical microbiology, School of basic medical science, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Dong
authors.affiliation: China National Tobacco Quality Supervision &Test Center, 2 Fengyang Street, Zhengzhou, Henan, 450001, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of medical microbiology, School of basic medical science, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, 230027, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, 230027, China.
authors.forename: Xiaqiong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of medical microbiology, School of basic medical science, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.affiliation: Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Han
authors.affiliation: School of Public Health, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Fan
authors.affiliation: Department of medical microbiology, School of basic medical science, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of medical microbiology, School of basic medical science, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Shili
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D000075747:Baculoviral IAP Repeat-Containing 3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D003652:Decanoic Acids / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D020382:Interleukin-18 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D003652:Decanoic Acids; D005466:Fluorocarbons; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D052003:NF-kappa B p52 Subunit; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; C036567:perfluorodecanoic acid; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D020170:Caspase 1