title: Regulation of ICAM-1 expression in gingival fibroblasts infected with high-glucose-treated P. gingivalis.
abstract: Porphyromonas gingivalis is a major pathogen in the initiation and progression of periodontal disease, which is recognized as a common complication of diabetes. ICAM-1 expression by human gingival fibroblasts (HGFs) is crucial for regulating local inflammatory responses in inflamed periodontal tissues. However, the effect of P. gingivalis in a high-glucose situation in regulating HGF function is not understood. The P. gingivalis strain CCUG25226 was used to study the mechanisms underlying the modulation of HGF ICAM-1 expression by invasion of high-glucose-treated P. gingivalis (HGPg). A high-glucose condition upregulated fimA mRNA expression in P. gingivalis and increased its invasion ability in HGFs. HGF invasion with HGPg induced increases in the expression of ICAM-1. By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of p38 MAPK and Akt pathways is critical for HGPg-induced ICAM-1 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that HGPg invasion increases NF-κB- and Sp1-DNA-binding activities in HGFs. Inhibition of NF-κB and Sp1 activations blocked the HGPg-induced ICAM-1 promoter activity and expression. The effect of HGPg on HGF signalling and ICAM-1 expression is mediated by CXC chemokine receptor 4 (CXCR4). Our findings identify the molecular pathways underlying HGPg-dependent ICAM-1 expression in HGFs, providing insight into the effect of P. gingivalis invasion in HGFs.
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Chang
authors.forename: Heng Jung
authors.initials: HJ
authors.lastname: Chen
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.forename: Tseng-Hsi
authors.initials: TH
authors.lastname: Lin
authors.forename: Ting-Ying
authors.initials: TY
authors.lastname: Huang
authors.forename: Chu-Shan
authors.initials: CS
authors.lastname: Choe
authors.forename: Li-Tsen
authors.initials: LT
authors.lastname: Lin
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000382:microbiology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D018799:Intercellular Adhesion Molecule-1; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose