title: Helicobacter pylori induces IL-1β and IL-18 production in human monocytic cell line through activation of NLRP3 inflammasome via ROS signaling pathway.
abstract: This study investigated whether Helicobacter pylori could activate the nucleotide-binding oligomerization domain-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome in human macrophages and the involvement of reactive oxygen species (ROS) in inflammasome activation. Phorbol-12-myristate-13-acetate (PMA)-differentiated human acute monocytic leukemia cell line THP-1 was infected with H. pylori. The levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in supernatant were measured by ELISA. Intracellular ROS level was analyzed by flow cytometry. Quantitative real-time PCR and western blot analysis were employed to determine the mRNA and protein expression levels of NLRP3 and caspase-1 in THP-1 cells, respectively. Our results showed that H. pylori infection could induce IL-1β and IL-18 production in PMA-differentiated THP-1 cells in a dose- and time-dependent manner. Moreover, secretion of IL-1β and IL-18 in THP-1 cells following H. pylori infection was remarkably reduced by NLRP3-specific small interfering RNA treatment. In addition, the intracellular ROS level was elevated by H. pylori infection, which could be eliminated by the ROS scavenger N-acetylcysteine (NAC). Furthermore, NAC treatment could inhibit NLRP3 inflammasome formation and caspase-1 activation and suppress the release of IL-1β and IL-18 from H. pylori-infected THP-1 cells. These findings provide novel insights into the innate immune response against H. pylori infection, which could potentially be used for the prevention and treatment of H. pylori-related diseases.
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Anyuan
authors.initials: A
authors.lastname: Liu
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Shuangyang
authors.initials: S
authors.lastname: Tang
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Yu
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, Hunan, China nhzhangyan@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000032:analysis; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; C000589760:IL18 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D020170:Caspase 1
keywords: Helicobacter pylori; IL-18; IL-1β; NLRP3; ROS; inflammasome