title: Porphyromonas gingivalis HSP60 peptides have distinct roles in the development of atherosclerosis.
abstract: Different epitope peptides of bacterial heat shock proteins may function as effector or regulatory molecules in autoimmune responses in infection-triggered atherosclerosis. We investigated the mechanisms for the distinct roles of two epitope peptides from Porphyromonas gingivalis heat shock protein 60 (HSP60) in atherogenesis with regard to peptide-specific T cell polarization relevant to (1) phenotype and cytokine profiles, (2) expression of transcription factors, and (3) role of antigen presenting dendritic cell subsets.Apolipoprotein E-knockout (ApoE KO) mice were immunized with peptide 14 or peptide 19 from P. gingivalis HSP60 prior to induction of atherosclerosis by infection with P. gingivalis plus a Western diet. Significant reductions in plaque/lipid droplet area and plasma cholesterol levels were observed in mice immunized with peptide 14, whereas the opposite phenomenon was evident in mice immunized with peptide 19. CD4+ T-cells polarized to the regulatory T-cell type in peptide 14-immunized group, whereas they polarized to the Th1 cells in peptide 19-immunized group; this observation was supported by the cytokine profiles characteristic to each T-cell phenotype.Significantly higher expression of Nr4a1 and Nr4a2 mRNA, transcriptional factors for regulatory T-cell type, were observed in peptide 14-immunized group. In contrast, the expression level of IFN-γ and T-bet mRNA, signaling molecules for Th1 cells, was higher in peptide 19-immunized group than in PBS-immunized group.In non-immunized wild mice, BMDC-derived CD11c+ dendritic cells have shown to stimulate Tregs significantly in antigen-nonspecific manner. However, each peptide antigen demonstrated a unique mode of preferential adoption of dendritic cell subsets.In conclusion, peptide 14 or peptide 19 from P. gingivalis HSP60, respectively, may play either an anti- or pro-atherogenic role in the ApoE KO mouse model of infection-triggered atherosclerosis through distinct mechanisms operating in the polarization of T cells.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, South Korea. eui kyong@pusan.ac.kr
authors.forename: Euikyong
authors.initials: E
authors.lastname: Jeong
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
authors.forename: June Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Go Sim
authors.initials: GS
authors.lastname: Cha
authors.forename: Sung-Jo
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Kang
authors.forename: Jeomil
authors.initials: J
authors.lastname: Choi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology*; D018834:Chaperonin 60 / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007114:Immunization; D015151:Immunoblotting; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D018834:Chaperonin 60; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D010455:Peptides