title: Heterogeneous Porphyromonas gingivalis LPS modulates immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in human gingival fibroblasts.
abstract: Periodontal (gum) disease is a highly prevalent infection and inflammation accounting for the majority of tooth loss in adult population worldwide. Porphyromonas gingivalis is a keystone periodontal pathogen and its lipopolysaccharide (PgLPS) acts as a major virulence attribute to the disease. Herein, we deciphered the overall host response of human gingival fibroblasts (HGFs) to two featured isoforms of tetra-acylated PgLPS1435/1449 and penta-acylated PgLPS1690 with reference to E. coli LPS through quantitative proteomics. This study unraveled differentially expressed novel biomarkers of immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in HGFs. PgLPS1690 greatly upregulated inflammatory proteins (e.g. cyclophilin, inducible nitric oxide synthase, annexins, galectin, cathepsins and heat shock proteins), whereas the anti-inflammatory proteins (e.g. Annexin A2 and Annexin A6) were significantly upregulated by PgLPS1435/1449. Interestingly, the antioxidants proteins such as mitochondrial manganese-containing superoxide dismutase and peroxiredoxin 5 were only upregulated by PgLPS1690. The cytoskeletal rearrangement-related proteins like myosin were differentially regulated by these PgLPS isoforms. The present study gives new insight into the biological properties of P. gingivalis LPS lipid A moiety that could critically modulate immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in HGFs, and thereby enhances our understanding of periodontal pathogenesis.
authors.affiliation: National Dental Centre Singapore, Singapore.|Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Thanuja D K
authors.initials: TDK
authors.lastname: Herath
authors.affiliation: School of Dentistry, University of Washington, Seattle, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Darveau
authors.affiliation: Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Chaminda J
authors.initials: CJ
authors.lastname: Seneviratne
authors.affiliation: School of Dentistry, University of California Los Angeles, Los Angeles, USA.
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Pharmacology &Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Jin
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005881:Gingiva / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity*; D016966:Porphyromonas gingivalis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides