PMID- 11748192
OWN - NLM
STAT- MEDLINE
DCOM- 20020114
LR  - 20210526
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 70
IP  - 1
DP  - 2002 Jan
TI  - Role for fimbriae and lysine-specific cysteine proteinase gingipain K in 
      expression of interleukin-8 and monocyte chemoattractant protein in Porphyromonas 
      gingivalis-infected endothelial cells.
PG  - 268-76
AB  - Recent cross-sectional and prospective epidemiological studies have demonstrated 
      an association between periodontal disease and atherosclerosis and human coronary 
      heart disease. Previously, we have established that the periodontal pathogen 
      Porphyromonas gingivalis is capable of invading aortic, heart, and human 
      umbilical vein endothelial cells (HUVEC). Since atherosclerosis is a chronic 
      inflammatory response initiated at the vascular wall, interactions of P. 
      gingivalis with endothelial cells and the subsequent host cell response to 
      infection may be important in the pathogenesis of atherosclerosis. In this study 
      we examined the consequences of P. gingivalis infection of HUVEC on the 
      expression of the chemokines interleukin-8 (IL-8) and monocyte chemotactic 
      protein 1 (MCP-1). HUVEC were found to constitutively produce low levels of IL-8 
      and MCP-1. The addition of P. gingivalis fimbrillin-specific peptides, 
      lipopolysaccharides (LPS), or heat-killed whole cell preparations to HUVEC 
      stimulated modest IL-8 and MCP-1 responses. In contrast, coculture of HUVEC with 
      live P. gingivalis strain A7436, 33277, or 381 abolished the IL-8 and MCP-1 
      responses. Inhibition of IL-8 and MCP-1 production was not dependent on bacterial 
      adherence since similar results were obtained with the nonadherent P. gingivalis 
      fimA mutant DPG3 or when P. gingivalis was preincubated with fimbrillin peptide 
      antisera prior to the addition to HUVEC. Furthermore, treatment of P. 
      gingivalis-infected HUVEC with cytochalsin D, which prevented P. gingivalis 
      invasion, also abolished the constitutive IL-8 and MCP-1 responses. Treatment of 
      HUVEC with E. coli LPS stimulated robust IL-8 and MCP-1 responses that were 
      abolished when stimulated cells were cocultured with live P. gingivalis. Analysis 
      of P. gingivalis-infected HUVEC cultures by an RNase protection assay revealed an 
      increase in the IL-8 transcript relative to uninfected HUVEC. Pretreatment of P. 
      gingivalis with protease inhibitors prior to the addition to HUVEC prevented the 
      inhibition of IL-8 and MCP-1 production in P. gingivalis-infected HUVEC, 
      indicating that the inhibition was proteolytically mediated. Coculture of HUVEC 
      with a P. gingivalis mutant deficient in lysine-specific cysteine proteinase 
      (gingipain K [Kgp]) resulted in an increase in both IL-8 transcription and 
      protein expression relative to that observed in HUVEC cocultured with the P. 
      gingivalis wild-type strain. These results indicate that P. gingivalis can 
      temporally modulate the chemokine response in endothelial cells through both 
      fimbriae and gingipain-mediated mechanisms.
FAU - Nassar, Hamdy
AU  - Nassar H
AD  - Department of Medicine, Boston University School of Medicine, Boston, 
      Massachusetts 02118, USA.
FAU - Chou, Hsin-Hua
AU  - Chou HH
FAU - Khlgatian, Mary
AU  - Khlgatian M
FAU - Gibson, Frank C 3rd
AU  - Gibson FC 3rd
FAU - Van Dyke, T E
AU  - Van Dyke TE
FAU - Genco, Caroline Attardo
AU  - Genco CA
LA  - eng
GR  - P01 DE013191/DE/NIDCR NIH HHS/United States
GR  - P01DE13191/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Gingipain Cysteine Endopeptidases)
RN  - 0 (Hemagglutinins)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptides)
RN  - 0 (fimbrillin)
RN  - 147680-16-8 (Fimbriae Proteins)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Adhesins, Bacterial
MH  - Amino Acid Sequence
MH  - Bacterial Adhesion/immunology
MH  - Bacterial Proteins/*immunology/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/*genetics
MH  - Cysteine Endopeptidases/genetics/*immunology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Endothelium, Vascular/cytology/*immunology/microbiology
MH  - Escherichia coli/metabolism
MH  - *Fimbriae Proteins
MH  - *Gene Expression
MH  - Gingipain Cysteine Endopeptidases
MH  - Heating
MH  - Hemagglutinins/genetics/*immunology
MH  - Humans
MH  - Interleukin-8/biosynthesis/*genetics
MH  - Lipopolysaccharides/immunology/pharmacology
MH  - Lysine
MH  - Molecular Sequence Data
MH  - Peptides/immunology/pharmacology
MH  - Pili, Sex/*immunology
MH  - Porphyromonas gingivalis/drug effects/*immunology/physiology
MH  - Transcription, Genetic
PMC - PMC127609
EDAT- 2001/12/19 10:00
MHDA- 2002/01/15 10:01
PMCR- 2002/01/01
CRDT- 2001/12/19 10:00
PHST- 2001/12/19 10:00 [pubmed]
PHST- 2002/01/15 10:01 [medline]
PHST- 2001/12/19 10:00 [entrez]
PHST- 2002/01/01 00:00 [pmc-release]
AID - 0676 [pii]
AID - 10.1128/IAI.70.1.268-276.2002 [doi]
PST - ppublish
SO  - Infect Immun. 2002 Jan;70(1):268-76. doi: 10.1128/IAI.70.1.268-276.2002.