PMID- 9846737
OWN - NLM
STAT- MEDLINE
DCOM- 19990401
LR  - 20210322
IS  - 1350-0872 (Print)
IS  - 1350-0872 (Linking)
VI  - 144 ( Pt 11)
DP  - 1998 Nov
TI  - A lipid A-associated protein of Porphyromonas gingivalis, derived from the 
      haemagglutinating domain of the RI protease gene family, is a potent stimulator 
      of interleukin 6 synthesis.
PG  - 3019-3026
LID - 10.1099/00221287-144-11-3019 [doi]
AB  - There is evidence that the lipid A-associated proteins (LAPs) of enteric bacteria 
      can induce the synthesis of interleukin 1 (IL-1) and therefore may be important 
      virulence factors. Porphyromonas gingivalis is now recognized as a major pathogen 
      in the chronic inflammatory periodontal diseases and it has previously been 
      reported that a crude LAP fraction from this organism could induce IL-1 and 
      interleukin 6 (IL-6) synthesis. In the present study the chemical and biological 
      properties of the LAPs of this bacterium have been further characterized. 
      Analysis by SDS-PAGE has shown that the LAPs comprise nine proteins of molecular 
      masses 81, 68, 48, 47, 28, 25, 20, 17 and 16 kDa. These LAPs, at concentrations 
      as low as 100 ng ml(-1), were shown to stimulate human gingival fibroblasts, 
      human peripheral blood mononuclear cells and whole human blood to produce the 
      pro-inflammatory cytokine IL-6. The cytokine-inducing activity of the LAPs was 
      reduced after heat-inactivation and trypsinization, suggesting that the activity 
      was not due to contaminating LPS. To establish which proteins in this mixture 
      were the active cytokine inducers, the LAPs were separated by electrophoresis on 
      polyacrylamide gels. The majority of the activity was associated with the 17 kDa 
      LAP. N-terminal sequence analysis demonstrated that this protein was homologous 
      to an internal region of a conserved adhesin domain contained within a family of 
      P. gingivalis extracellular proteins including the RI protease, Lys-gingipain, 
      porphypain and haemagglutinin A. In addition to a role in adherence, the adhesin 
      domain(s) of these proteins may also have cytokine-inducing properties. 
      Furthermore, it has also been shown that the previously observed degradation of 
      cytokines by P. gingivalis may be attributable to the catalytic domain of the RI 
      protease. Thus, different domains within the same molecule appear to have 
      opposing actions on pro-inflammatory cytokine levels and the balance between 
      these two activities may influence the cytokine status of the periodontium in 
      patients with the common chronic inflammatory conditions known as the periodontal 
      diseases.
FAU - Sharp, Lindsay
AU  - Sharp L
AD  - Cellular Microbiology Research Group and Microbiology University College London, 
      256 Gray's Inn Road, London WClX 8LD, UK.
FAU - Poole, Stephen
AU  - Poole S
AD  - >Division of Endocrinology, National Institute for Biological Standards and 
      Control, Blanche Lane, South Mimms, Potters Bar EN6 3QG, UK.
FAU - Reddi, Krisanavane
AU  - Reddi K
AD  - Department, Eastman Dental Institute, University College London, 256 Gray's Inn 
      Road, London WClX 8LD, UK.
FAU - Fletcher, Julie
AU  - Fletcher J
AD  - Department, Eastman Dental Institute, University College London, 256 Gray's Inn 
      Road, London WClX 8LD, UK.
FAU - Nair, Sean
AU  - Nair S
AD  - Cellular Microbiology Research Group and Microbiology University College London, 
      256 Gray's Inn Road, London WClX 8LD, UK.
FAU - Wilson, Michael
AU  - Wilson M
AD  - Department, Eastman Dental Institute, University College London, 256 Gray's Inn 
      Road, London WClX 8LD, UK.
FAU - Curtis, Michael
AU  - Curtis M
AD  - Department of Oral Microbiology, Medical Research Council Molecular Pathogenesis 
      Group, The Royal London School of Medicine and Dentistry, London E l 2AA, UK.
FAU - Henderson, Brian
AU  - Henderson B
AD  - Cellular Microbiology Research Group and Microbiology University College London, 
      256 Gray's Inn Road, London WClX 8LD, UK.
FAU - Tabonal, Peter
AU  - Tabonal P
AD  - Cellular Microbiology Research Group and Microbiology University College London, 
      256 Gray's Inn Road, London WClX 8LD, UK.
LA  - eng
SI  - SWISSPROT/P81411
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Microbiology (Reading)
JT  - Microbiology (Reading, England)
JID - 9430468
RN  - 0 (Bacterial Proteins)
RN  - 0 (Endotoxins)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipid A)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (lipid A-associated protein, Bacteria)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Bacterial Proteins/chemistry/*immunology
MH  - Bacteroidaceae Infections/microbiology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Endopeptidases/genetics/metabolism
MH  - Endotoxins/chemistry/*immunology
MH  - Fibroblasts/immunology
MH  - Gingiva
MH  - Humans
MH  - Interleukin-1/metabolism
MH  - Interleukin-6/*biosynthesis/blood
MH  - Lipid A/chemistry/*immunology
MH  - Lipopolysaccharides/pharmacology
MH  - Molecular Sequence Data
MH  - Periodontal Diseases/microbiology
MH  - Porphyromonas gingivalis/*immunology
EDAT- 1998/12/10 00:00
MHDA- 1998/12/10 00:01
CRDT- 1998/12/10 00:00
PHST- 1998/12/10 00:00 [pubmed]
PHST- 1998/12/10 00:01 [medline]
PHST- 1998/12/10 00:00 [entrez]
AID - 10.1099/00221287-144-11-3019 [doi]
PST - ppublish
SO  - Microbiology (Reading). 1998 Nov;144 ( Pt 11):3019-3026. doi: 
      10.1099/00221287-144-11-3019.