Porphyromonas gingivalis fimbriae-dependent interleukin-6 autocrine regulation by increase of gp130 in endothelial cells.
OBJECTIVE
Local persistent infection by Porphyromonas gingivalis leads to inflammatory systemic diseases, such as atherosclerosis. We have reported previously that avirulent P. gingivalis fimbriae-dependent invasion into endothelial cells might be involved in progression of atherosclerosis. Although interleukin-6 (IL-6) regulates progression of atherosclerosis, little is known about the relationship of P. gingivalis fimbriae-dependent invasion to IL-6 regulation in endothelial cells.


METHODS
We examined the secretion of IL-6 and the expression of the IL-6 signal transducer gp130 in human umbilical vein endothelial cells (HUVEC) infected with the wild-type FDC381 strain of P. gingivalisand a fimbriae-deficient mutant (fimA) by enzyme-linked immunosorbent assay, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry (fluorescence-activated cell sorting, FACS) analysis.


RESULTS
Coculture of HUVEC with P. gingivalis resulted in increase of IL-6 secretion at 24 h postinfection. Interestingly, the increase was inhibited significantly in HUVEC infected with the P. gingivalis fimA mutant. In addition, the increase of IL-6 secretion induced by P. gingivalis infection was significantly impaired by the meiosis specific kinase 1 inhibitor, PD98059, or the nuclear factor kappaB inhibitor, Bay11-7082. Furthermore, we demonstrated that gp130 expression increased with P. gingivalis infection. Importantly, gp130 expression was significantly impaired by P gingivalis fimA mutant infection compared with wild-type P. gingivalis infection, as assessed by both quantitative RT-PCR and FACS analysis.


CONCLUSIONS
Our findings indicate that P. gingivalis fimbriae are important factors in the autocrine regulation of IL-6, by increasing gp130 in endothelial cells.
Ho
Y-S
YS
Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei, Taiwan.
Lai
M-T
MT
Liu
S-J
SJ
Lin
C-T
CT
Naruishi
K
K
Takashiba
S
S
Chou
H-H
HH
D019898:Autocrine Communication / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D018920:Coculture Techniques; D050822:Cytokine Receptor gp130 / Q000032:analysis / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology* / Q000382:microbiology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000276:immunology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D018933:Pili, Sex / Q000235:genetics / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology*; D013450:Sulfones / Q000494:pharmacology; D014471:Umbilical Veins / Q000473:pathology
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015850:Interleukin-6; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; C063055:fimbrillin; D050822:Cytokine Receptor gp130; D036781:Fimbriae Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one