scholarly journals BAY11‑7082 inhibits the expression of tissue factor and plasminogen activator inhibitor‑1 in type‑II alveolar epithelial cells following TNF‑α stimulation via the NF‑κB pathway

2020 ◽  
Vol 21 (2) ◽  
Author(s):  
Yumei Cheng ◽  
Bo Liu ◽  
Hong Qian ◽  
Huilin Yang ◽  
Yahui Wang ◽  
...  
1991 ◽  
Vol 260 (4) ◽  
pp. L286-L295 ◽  
Author(s):  
T. J. Gross ◽  
R. H. Simon ◽  
C. J. Kelly ◽  
R. G. Sitrin

There is considerable evidence to suggest that intra-alveolar plasminogen activation is instrumental in many aspects of inflammatory lung injury and subsequent tissue repair. Rat alveolar epithelial cells produce large quantities of urokinase-type plasminogen activator (uPA) in vitro, and uPA expression is modulated in association with cellular differentiation and exposure to inflammatory mediators. We now report that these cells also secrete heat-stable PA inhibitory activity having the characteristics of PA inhibitor type 1 (PAI-1). In particular, immunoreactive PAI-1 was demonstrable in conditioned media, cell lysates, and extracellular matrix from epithelial cell cultures. As alveolar epithelial cells differentiated in vitro, secreted PA inhibitor activity increased significantly from 104 +/- PAI U/ml (n = 5, mean +/- SE) on day 2 to 442 +/- 150 on day 7 in parallel with increases in secreted and matrix-associated immunoreactive PAI-1. PAI-1 mRNA expression decreased over this same period suggesting posttranscriptional regulation. The levels of both newly synthesized antigen and PAI-1 mRNA were increased by exposure to lipopolysaccharide and tumor necrosis factor-alpha. Thus, by the coexpression of uPA and PAI-1, the alveolar epithelium may actively regulate the generation of plasmin in both the normal and injured alveolus.


2013 ◽  
Vol 7 (5) ◽  
pp. 403-411 ◽  
Author(s):  
Earl Gillespie ◽  
Susan E. Leeman ◽  
Luisa A. Watts ◽  
Jennifer A. Coukos ◽  
Michael J. O'Brien ◽  
...  

1999 ◽  
Vol 143 (1) ◽  
pp. 81-90 ◽  
Author(s):  
M. Cigolini ◽  
M. Tonoli ◽  
L. Borgato ◽  
L. Frigotto ◽  
F. Manzato ◽  
...  

1995 ◽  
Vol 108 (6) ◽  
pp. 2361-2368 ◽  
Author(s):  
S. Stefansson ◽  
M.Z. Kounnas ◽  
J. Henkin ◽  
R.K. Mallampalli ◽  
D.A. Chappell ◽  
...  

Glycoprotein 330 (gp330) is a member of a family of receptors related to the low density lipoprotein receptor (LDLR). Although several ligands have been shown to bind gp330 in solid-phase assays, the ability of gp330 to mediate ligand endocytosis has not been demonstrated. To develop a cellular model for gp330 function we screened a variety of cultured cell lines and identified several that expressed this protein, including immortalized rat type II pneumocytes and a human and two rodent tumor cell lines. Using type II pneumocytes, endocytosis of a previously described gp330 ligand, urokinase (uPA) complexed with plasminogen activator inhibitor-1 (uPA:PAI-1) and two new ligands, PAI-1 and pro-uPA, was demonstrated. RAP, the 39 kDa receptor-associated protein known to antagonize ligand binding to gp330 in solid-phase binding assays, completely inhibited both internalization and degradation of the radiolabeled ligands by type II pneumocytes. This suggested that the clearance of these ligands was dependent on either gp330 or the LDLR-related protein (LRP), which shares several ligand-binding characteristics with gp330. By using polyclonal antibodies to gp330, the cellular internalization and degradation of the ligands were inhibited by 30–50%; remaining ligand internalization and degradation activity could be partially inhibited by polyclonal antibodies against LRP. These findings indicate that gp330, like other LDLR family members, mediates endocytosis of its ligands. In addition, gp330 acts in concert with LRP in type II pneumocytes to mediate clearance of a variety of proteins involved in plasminogen activation, including uPA:PAI-1 complexes PAI-1 and pro-uPA.(ABSTRACT TRUNCATED AT 250 WORDS)


2011 ◽  
Vol 9 (3) ◽  
pp. 531-539 ◽  
Author(s):  
P. SEN ◽  
A. A. KOMISSAROV ◽  
G. FLOROVA ◽  
S. IDELL ◽  
U. R. PENDURTHI ◽  
...  

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