title: Proteomic mapping of stimulus-specific signaling pathways involved in THP-1 cells exposed to Porphyromonas gingivalis or its purified components.
abstract: Periodontitis is an inflammatory disease initiated by host-parasite interactions which contributes to connective tissue destruction and alveolar bone resorption. Porphyromonas gingivalis (P.g.), a black-pigmented Gram-negative anaerobic bacterium, is a major pathogen in the development and progression of periodontitis. To characterize the role that P. gingivalis and its cell surface components play in disease processes, we investigated the differential expression of proteins induced by live P.g., P.g. LPS, and P.g. FimA, using two-dimensional gel electrophoresis in combination with mass spectrometry. We have tested whether, at the level of protein expression, unique signaling pathways are differentially induced by the bacterial components P.g. LPS and P.g. FimA, as compared to live P.g. We found that P.g. LPS stimulation of THP-1 up-regulated the expression of a set of proteins compared to control: deoxyribonuclease, actin, carbonic anhydrase 2, alpha enolase, adenylyl cyclase-associated protein (CAP1), protein disulfide isomerase (PDI), glucose regulated protein (grp78), and 70-kDa heat shock protein (HSP70), whereas FimA treatment did not result in statistically significant changes to protein levels versus the control. Live P.g. stimulation resulted in 12 differentially expressed proteins: CAP1, tubulin beta-2 chain, ATP synthase beta chain, tubulin alpha-6 chain, PDI, vimentin, 60-kDa heat shock protein, and nucleolin were found to be up-regulated, while carbonic anhydrase II, beta-actin, and HSP70 were down-regulated relative to control. These differential changes by the bacteria and its components are interpreted as preferential signal pathway activation in host immune/inflammatory responses to P.g. infection.
authors.affiliation: Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Saba
authors.forename: Mark E
authors.initials: ME
authors.lastname: McComb
authors.forename: Donna L
authors.initials: DL
authors.lastname: Potts
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.forename: Salomon
authors.initials: S
authors.lastname: Amar
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D036781:Fimbriae Proteins / Q000276:immunology / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D018832:Molecular Chaperones / Q000032:analysis / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000032:analysis / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000276:immunology*; D019704:Protein Disulfide-Isomerases / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; D011506:Proteins; D025521:Tumor Suppressor Proteins; C063055:fimbrillin; D036781:Fimbriae Proteins; D024402:Carbonic Anhydrase II; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase; D019704:Protein Disulfide-Isomerases