IL-1beta increases uPA and uPA receptor expression in human gingival fibroblasts.
The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) in various cell types has been proposed as an important feature of many cellular processes requiring extracellular proteolysis, cell adhesion, motility, and invasion. uPAR attaches to the cell surface with a glycosylphophatidylinositol (GPI) anchor, and serves to localize and accelerate the proteolysis cascade. In this study, we examined both uPA and uPAR levels in human gingival fibroblasts treated with an inflammatory cytokine, interleukin-1beta (IL-1beta). PA activity in the cell lysate was increased by treatment with IL-1beta. Further, PA activity released by phosphatidylinositol-specific phospholipase C, which detaches the GPI anchor, was also increased by IL-1beta. The activity was inhibited by amiloride, a specific inhibitor of uPA. In addition, IL-1beta increased the protein and mRNA levels of both uPA and uPAR in gingival fibroblasts. These findings suggest that the enhancement of uPA and uPAR levels by IL-1beta may play an important role in the progression of periodontal diseases through pericellular proteolysis, and subsequent cellular behavior.
Ogura
N
N
Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan. nogura@mascat.nihon-u.ac.jp
Tobe
M
M
Tamaki
H
H
Nagura
H
H
Abiko
Y
Y
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D015533:Transcriptional Activation; D010738:Type C Phospholipases / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D018836:Inflammation Mediators; D007375:Interleukin-1; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D014568:Urokinase-Type Plasminogen Activator; D043265:Phosphatidylinositol Diacylglycerol-Lyase