PMID- 17299802
OWN - NLM
STAT- MEDLINE
DCOM- 20070727
LR  - 20131121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 212
IP  - 1
DP  - 2007 Jul
TI  - Actinobacillus actinomycetemcomitans lipopolysaccharide regulates matrix 
      metalloproteinase, tissue inhibitors of matrix metalloproteinase, and plasminogen 
      activator production by human gingival fibroblasts: a potential role in 
      connective tissue destruction.
PG  - 189-94
AB  - Fibroblasts, a major constituent of gingival connective tissue, can produce 
      immunoregulatory cytokines and proteolytic enzymes that may contribute to tissue 
      destruction. In this study, we evaluated the production of matrix 
      metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and plasminogen 
      activators by gingival fibroblasts stimulated with lipopolysaccharides (LPS) 
      produced by periodontopathogens, including Actinobacillus actinomycetemcomitans. 
      In addition, changes in the expression and phosphorylation state of fibroblast 
      intracellular signaling proteins induced by A. actinomycetemcomitans LPS were 
      characterized using antibody microarrays. We showed that A. actinomycetemcomitans 
      LPS induced the production of a 50 kDa plasminogen activator, MMP-2 and, to a 
      lesser extent, MMP-3 by fibroblasts. The stimulation of fibroblasts with A. 
      actinomycetemcomitans LPS also resulted in the overproduction of TIMP-1, but had 
      no effect on the production of TIMP-2. Comparable responses were also obtained 
      with Porphyromonas gingivalis and Fusobacterium nucleatum subsp. nucleatum LPS. 
      The results of the microarray analyses showed that A. actinomycetemcomitans LPS 
      induced changes in the phosphorylation state and expression of gingival 
      fibroblast intracellular signaling proteins. More specifically, they suggested 
      that A. actinomycetemcomitans LPS may induce both Jun N-terminus protein-serine 
      kinases (JNK) and mitogen-activated protein-serine kinase p38 alpha (p38alpha 
      MAPK) pathway activation, leading to increased activator protein-1 (AP-1) and 
      nuclear factor kappa-B (NFkappaB) activities, which in turn can stimulate MMP-2, 
      MMP-3, TIMP-1, and urokinase-type plasminogen activator (uPA) expression. This 
      may contribute to periodontal connective tissue destruction.
FAU - Bodet, Charles
AU  - Bodet C
AD  - Groupe de Recherche en Ecologie Buccale, Faculte de Medecine Dentaire, Universite 
      Laval, Quebec City, Quebec, Canada.
FAU - Andrian, Elisoa
AU  - Andrian E
FAU - Tanabe, Shin-Ichi
AU  - Tanabe S
FAU - Grenier, Daniel
AU  - Grenier D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Aggregatibacter actinomycetemcomitans/*metabolism
MH  - Cell Line
MH  - Connective Tissue Diseases/metabolism
MH  - Fibroblasts/drug effects/metabolism
MH  - Fusobacterium nucleatum/metabolism
MH  - Gingiva/cytology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Matrix Metalloproteinase 2/genetics/*metabolism
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Porphyromonas gingivalis/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/*metabolism
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
MH  - Urokinase-Type Plasminogen Activator/genetics/*metabolism
EDAT- 2007/02/15 09:00
MHDA- 2007/07/28 09:00
CRDT- 2007/02/15 09:00
PHST- 2007/02/15 09:00 [pubmed]
PHST- 2007/07/28 09:00 [medline]
PHST- 2007/02/15 09:00 [entrez]
AID - 10.1002/jcp.21018 [doi]
PST - ppublish
SO  - J Cell Physiol. 2007 Jul;212(1):189-94. doi: 10.1002/jcp.21018.