title: Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts.
abstract: The NLRP3/caspase-1 inflammasome pathway plays an important role in cellular immune defence against bacterial infection; however, its function in human dental pulp tissue and human dental pulp fibroblasts remains poorly understood. We demonstrate that NLRP3 protein expression occurs to a greater extent in pulp tissue with irreversible pulpitis than in normal pulp tissue and in tissue with reversible pulpitis. Caspase-1 is present in its active (cleaved) form only in pulp tissue with irreversible pulpitis. NLRP3 and caspase-1 are expressed in the odontoblast layers in normal human dental pulp tissue, whereas in inflamed pulp tissue, the odontoblast layers are disrupted and dental pulp cells are positive for NLRP3 and caspase-1. Additionally, we investigate the role of the NLRP3/caspase-1 inflammasome pathway in human dental pulp fibroblasts and show that ATP activates the P2X7 receptor on the cell membrane triggering K(+) efflux and inducing the gradual recruitment of the membrane pore pannexin-1. Extracellular lipopolysaccharide is able to penetrate the cytosol and activate NLRP3. Furthermore, the low intracellular K(+) concentration in the cytosol triggers reactive oxygen species generation, which also induces the NLRP3 inflammasome. Thus, the NLRP3/caspase-1 pathway has a biological role in the innate immune response mounted by human dental pulp fibroblasts.
authors: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 710032, Shaanxi, People's Republic of China.
authors: Wenkai
authors: W
authors: Jiang
authors: Haipeng
authors: H
authors: Lv
authors: Haijing
authors: H
authors: Wang
authors: Diya
authors: D
authors: Wang
authors: Shukai
authors: S
authors: Sun
authors: Qian
authors: Q
authors: Jia
authors: Peina
authors: P
authors: Wang
authors: Bing
authors: B
authors: Song
authors: Longxing
authors: L
authors: Ni
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology; D000293:Adolescent; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology*; D020170:Caspase 1 / Q000032:analysis / Q000276:immunology*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000032:analysis / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000032:analysis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000276:immunology; D058486:Receptors, Purinergic P2X7 / Q000032:analysis / Q000276:immunology; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D020170:Caspase 1