title: Sterol Regulatory Element-Binding Protein-1c Regulates Inflammasome Activation in Gingival Fibroblasts Infected with High-Glucose-TreatedPorphyromonas gingivalis.
abstract: Background:Porphyromonas gingivalisis a major bacterial species implicated in the progression of periodontal disease, which is recognized as a common complication of diabetes. The interleukin (IL)-1β, processed by the NLR family pyrin domain containing 3 (NLRP3) inflammasome, has been identified as a target for pathogenic infection of the inflammatory response. However, the effect ofP. gingivalisin a high-glucose situation in the modulation of inflammasome activation in human gingival fibroblasts (HGFs) is not well-understood.Methods:P. gingivalisstrain CCUG25226 was used to study the mechanisms underlying the regulation of HGF NLRP3 expression by the infection of high-glucose-treatedP. gingivalis(HGPg).Results:HGF infection with HGPg increases the expression of IL-1β and NLRP3. We further demonstrated that the upregulation of sterol regulatory element-binding protein (SREBP)-1c by activation of the Akt and p70S6K pathways is critical for HGPg-induced NLRP3 expression. We showed that the inhibition of Janus kinase 2 (JAK2) blocks the Akt- and p70S6K-mediated SREBP-1c, NLRP3, and IL-1β expression. The effect of HGPg on HGF signaling and NLRP3 expression is mediated by β1 integrin. In addition, gingival tissues from diabetic patients with periodontal disease exhibited higher NLRP3 and SREBP-1c expression.Conclusions:Our findings identify the molecular pathways underlying HGPg-dependent NLRP3 inflammasome expression in HGFs, providing insight into the effect ofP. gingivalisinvasion in HGFs.
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology (CGUST)Chiayi, Taiwan; Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology (CGUST)Taoyuan, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology (CGUST)Chiayi, Taiwan.
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital Chiayi, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.affiliation: Division of Nephrology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Te-Chuan
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital - Kaohsiung Medical Center Kaohsiung, Taiwan.
authors.forename: Ko-Chao
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital Chiayi, Taiwan.
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University Chiayi, Taiwan.
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital - Kaohsiung Medical CenterKaohsiung, Taiwan; Graduate Institute of Clinical Medical Science, Chang Gung University College of MedicineKaohsiung, Taiwan.
authors.forename: Hong-Ren
authors.initials: HR
authors.lastname: Yu
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology* / Q000382:microbiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000096:biosynthesis*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D005947:Glucose
keywords: NLRP3; Porphyromonas gingivalis; SREBP-1c; gingival fibroblasts; high glucose