IADR Abstract Archives
PCSK9 Induction by P. gingivalis in Dependent of Inflammatory Response
Objectives: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine protease regulating low-density lipoprotein (LDL) cholesterol levels by degradation of LDL receptor, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9, especially property of bacterial components to induce PCSK9 are largely unknown. The aim of present study is to analyze the property of nucleic acid antigens for induction of PCSK9 using murine model.
Methods: C57BL/6 mice (wild-type) and Unc93b1 mice (3d), deficient in sensing nucleic acid antigens, were intraperitoneally infected with P. gingivalis strain W83 or Toll like receptor 3, 7, and 9 specific nucleic acid antigens (Poly I:C, R848, CpG-DNA). Gene expressions of PCSK9, Type I interferon, and TNF-α in the lever were analyzed by quantitative PCR. Serum PCSK9 levels were measured by ELISA. All the protocol of animal experiments were approved by the institutional committee of Niigata University.
Results: P. gingivalis infection induced significant elevation of serum PCSK9 in wild-type and 3d. However, the elevation of PCSK9 was significantly reduced in 3d compared with wild-type (P <0.01). Administration of R848 and CpG-DNA, but not Poly (I:C) induced serum PCSK9 in wild-type (P <0.05 and P <0.01, respectively), in spite of the gene expressions of TNF-α in liver in administration of each compounds.
Conclusions: PCSK9 is induced by sensing nucleic antigens by TLR7 and TLR9 but not TLR3. The lack of PCSK9 induction with remained up-regulation of TNF-α gene indicates that PCSK9 is not induced by inflammatory response directly.
Methods: C57BL/6 mice (wild-type) and Unc93b1 mice (3d), deficient in sensing nucleic acid antigens, were intraperitoneally infected with P. gingivalis strain W83 or Toll like receptor 3, 7, and 9 specific nucleic acid antigens (Poly I:C, R848, CpG-DNA). Gene expressions of PCSK9, Type I interferon, and TNF-α in the lever were analyzed by quantitative PCR. Serum PCSK9 levels were measured by ELISA. All the protocol of animal experiments were approved by the institutional committee of Niigata University.
Results: P. gingivalis infection induced significant elevation of serum PCSK9 in wild-type and 3d. However, the elevation of PCSK9 was significantly reduced in 3d compared with wild-type (P <0.01). Administration of R848 and CpG-DNA, but not Poly (I:C) induced serum PCSK9 in wild-type (P <0.05 and P <0.01, respectively), in spite of the gene expressions of TNF-α in liver in administration of each compounds.
Conclusions: PCSK9 is induced by sensing nucleic antigens by TLR7 and TLR9 but not TLR3. The lack of PCSK9 induction with remained up-regulation of TNF-α gene indicates that PCSK9 is not induced by inflammatory response directly.