Increase of urokinase-type plasminogen activator receptor expression in human gingival fibroblasts by Porphyromonas gingivalis lipopolysaccharide. 1999

N Ogura, and H Nagura, and Y Abiko
Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan. nogura@mascat.nihon-u.ac.jp

BACKGROUND Urokinase-type plasminogen activator receptor (uPAR) presenting on the cell surface with glycosylphosphatidylinositol (GPI) anchor is a key component in the plasminogen activator (PA)-plasmin system and plays a critical role in extracellular matrix degradation. It is believed that uPAR serves to localize and accelerate this generation system. In this study, we examined the levels of both uPA and uPAR in human gingival fibroblasts treated with Porphyromonas gingivalis lipopolysaccharide (LPS). METHODS Human gingival fibroblasts from the seventh to tenth doubling passages were plated at 5x10(4) cells per well in 24-well plates. The confluent-stage cells were cultured for 24 hours in alpha-MEM medium containing 2% fetal calf serum, after which they were incubated with P. gingivalis LPS. PA activity was measured using plasminogen and plasmin substrate S2251. RESULTS PA activity in the cell lysate was increased by LPS and reached maximum at 1 microg/ml LPS after being incubated for 8 hours. PA activity released by phosphatidylinositol-specific phospholipase C, which detaches the GPI anchor, was also increased by LPS. The activity was inhibited by amiloride, which is a specific inhibitor for uPA. LPS increased the protein and mRNA levels of both uPA and uPAR in gingival fibroblasts. CONCLUSIONS These findings suggest that increase of the uPAR level by LPS may play an important role in the progression of periodontal diseases through pericellular proteolysis.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D010510 Periodontal Diseases Pathological processes involving the PERIODONTIUM including the gum (GINGIVA), the alveolar bone (ALVEOLAR PROCESS), the DENTAL CEMENTUM, and the PERIODONTAL LIGAMENT. Parodontosis,Pyorrhea Alveolaris,Disease, Periodontal,Diseases, Periodontal,Parodontoses,Periodontal Disease
D010960 Plasminogen Activators A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. Extrinsic Plasminogen Activators,Plasminogen Activator,Uterine-Tissue Plasminogen Activator,Uterine Tissue Plasminogen Activator
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005881 Gingiva Oral tissue surrounding and attached to TEETH. Gums,Interdental Papilla,Papilla, Interdental,Gum
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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