CGP-42112 partially activates human monocytes and reduces their stimulation by lipopolysaccharides

1997 ◽  
Vol 273 (3) ◽  
pp. C826-C833 ◽  
Author(s):  
G. Egidy ◽  
J. Friedman ◽  
M. Viswanathan ◽  
L. M. Wahl ◽  
J. M. Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Matrix Metalloproteinase ◽  
Transforming Growth Factor ◽  
Matrix Metalloproteinase 9 ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Binding Studies ◽  
Metalloproteinase 9 ◽  
At2 Receptors

CGP 42112, a high-affinity ligand for angiotensin II AT2 receptors, binds to rat macrophage/microglia lacking AT2 receptors. Here we report that CGP-42112 binds to human monocytes and exerts specific effects. Binding studies revealed a single site, highly specific for CGP-42112, not displaceable by angiotensin II, angiotensin fragments, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-10, transforming growth factor-beta, or lipopolysaccharide (LPS). Incubation of purified human monocytes in serum-free medium with CGP-42112 enhanced, in a dose-dependent manner, cell attachment to fibronectin and collagen-coated dishes as well as matrix metalloproteinase-9 secretion. CGP-42112 did not promote cytokine secretion. In contrast, when added in the presence of low doses of LPS, CGP-42112 reduced the LPS-stimulated secretion of TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 without affecting IL-10 and decreased the LPS-stimulated matrix metalloproteinase-9 activity. Additionally, CGP-42112 inhibited the increase in protein kinase A activity produced by LPS. Our results indicate that CGP-42112 may modulate monocyte activation through binding to a novel receptor.

scholarly journals SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jelena Kocić ◽  
Victor Villar ◽  
Aleksandra Krstić ◽  
Juan F. Santibanez
Keyword(s):  
Matrix Metalloproteinase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Regulatory Protein ◽  
Mek Inhibitor ◽  
Matrix Metalloproteinase 9 ◽  
Transformed Cells ◽  
Interacting Protein ◽  
Metalloproteinase 9

Transforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-β1-induced MMP-9 production. Mouse transformed keratinocytes (PDV) were stably transfected with SKIP antisense construct. We observed that SKIP depletion provoked an enhancement in the expression of MMP-9 in response to TGF-β1 treatment. The downregulation of SKIP produced an enhancement in TGF-β1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-β1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP-9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a regulatory protein in TGF-β1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells.

Important role of the angiotensin II pathway in producing matrix metalloproteinase-9 in human thoracic aortic aneurysms

2013 ◽  
Vol 183 (1) ◽  
pp. 472-477 ◽  
Author(s):  
Ayako Nagasawa ◽  
Koichi Yoshimura ◽  
Ryo Suzuki ◽  
Akihito Mikamo ◽  
Osamu Yamashita ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 9 ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms ◽  
Metalloproteinase 9

Thrombin regulates matrix metalloproteinase-9 expression in human monocytes

2009 ◽  
Vol 385 (2) ◽  
pp. 241-246 ◽  
Author(s):  
Chi-Jen Chang ◽  
Lung-An Hsu ◽  
Yu-Hsein Ko ◽  
Pei-Ling Chen ◽  
Yi-Ting Chuang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 9 ◽  
Human Monocytes ◽  
Metalloproteinase 9

scholarly journals CD14 Mediates Cross Talk between Mononuclear Cells and Fibroblasts for Upregulation of Matrix Metalloproteinase 9 by Borrelia burgdorferi

2007 ◽  
Vol 75 (6) ◽  
pp. 3062-3069 ◽  
Author(s):  
Zhihui Zhao ◽  
Rhonda Fleming ◽  
Bilaal McCloud ◽  
Mark S. Klempner
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Matrix Metalloproteinase ◽  
Mononuclear Cells ◽  
Erythema Migrans ◽  
Matrix Metalloproteinase 9 ◽  
Dependent Manner ◽  
U937 Cells ◽  
Concentration Dependent Manner ◽  
Metalloproteinase 9

ABSTRACT Lyme disease is an infection caused by a tick-borne spirochete, Borrelia burgdorferi. Matrix metalloproteinase 9 (MMP-9) was selectively upregulated in the erythema migrans skin lesions of patients with acute Lyme disease. In this study, the mechanism of upregulation of MMP-9 was investigated in vitro and in vivo. The concentrations of MMP-9 and soluble CD14 were markedly elevated in serum from patients with acute Lyme disease and were also upregulated in U937 cells by B. burgdorferi in a time- and concentration-dependent manner. MMP-9 mRNA was expressed at baseline in fibroblasts in the presence or absence of B. burgdorferi. However, when fibroblasts were incubated with supernatants from U937 cells with B. burgdorferi or recombinant CD14, the expression of MMP-9 was significantly increased. This effect was completely abolished by the anti-CD14 antibody. These data suggest that the upregulation of MMP-9 by B. burgdorferi involves the CD14 pathway in infiltrating inflammatory cells. Fibroblasts could be recruited to amplify local production of MMP-9 by acquiring CD14 from macrophages.

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