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

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.

2003 ◽  
Vol 188 (8) ◽  
pp. 1098-1104 ◽  
Author(s):  
Zhihui Zhao ◽  
Hernan Chang ◽  
Richard P. Trevino ◽  
Kara Whren ◽  
Jag Bhawan ◽  
...  

Author(s):  
Lucas C. Klemm ◽  
Evan Czerwonka ◽  
Mary L. Hall ◽  
Philip G. Williams ◽  
Alejandro M.S. Mayer

Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro [1]. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S. javanicum or S. ocellatum LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O2−), matrix metalloproteinase-9 (MMP-9) and cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either S. javanicum LPS, S. ocellatum LPS, or E. coli LPS (positive control) in a concentration-dependent manner for 18 hours at 35.9 °C. We observed that treatment of microglia with either E. coli LPS, S. javanicum or S. ocellatum LPS generated statistically significant and concentration-dependent O2−, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both S. javanicum and S. ocellatum LPS elicited classical and alternative activation of microglia and concomitant release of O2-, MMP-9 and cytokines and chemokines in a concentration-dependent manner. To our knowledge this is the first report on the toxicity of cyanobacteria S. javanicum and S. ocellatum LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system. 


Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4946-4953 ◽  
Author(s):  
Ben J. Gu ◽  
James S. Wiley

Abstract Matrix metalloproteinase-9 (MMP-9) activity is required for inflammatory response, leukocyte recruitment, and tumor invasion. There is increasing evidence suggesting that the P2X7 receptor of mononuclear cells, which is activated by extracellular adenosine triphosphate (ATP), is involved in inflammatory responses. In this study, ATP caused a rapid release of MMP-9 and a moderate decrease in tissue inhibitor of metalloproteinase 1 (TIMP-1) release from human peripheral-blood mononuclear cells (PBMCs) over a 30-minute time course. The release was time- and dose-dependent and dissociated from ATP-induced cell death. BzATP, which is the most potent agonist for the P2X7 receptor, also caused a similar effect at a lower dosage. ATP-induced MMP-9 release was inhibited by the P2X7 receptor antagonists periodate oxidized ATP and KN-62, or by calcium chelators, as well as by a loss-of-function polymorphism in the P2X7 receptor, but not by brefeldin A, monensin, or cycloheximide, or by anti–tumor necrosis factor-α (TNF-α) or anti–interleukin-1β (IL-1β) monoclonal antibodies. Results from purified subsets of PBMCs showed monocytes were the major source for MMP-9 and TIMP-1 release, and ATP remained effective in purified monocyte and T-cell populations. These observations suggest a novel role for P2X7 as a pro-inflammatory receptor involved in rapid MMP-9 release and leukocyte recruitment.


2003 ◽  
Vol 33 (7) ◽  
pp. 555-560 ◽  
Author(s):  
K. B. Holven ◽  
B. Halvorsen ◽  
H. Schulz ◽  
P. Aukrust ◽  
L. Ose ◽  
...  

2009 ◽  
Vol 77 (7) ◽  
pp. 2643-2649 ◽  
Author(s):  
Andrew J. Heilpern ◽  
Warren Wertheim ◽  
Jia He ◽  
George Perides ◽  
Roderick T. Bronson ◽  
...  

ABSTRACT Borrelia burgdorferi, the causative agent of Lyme arthritis, does not produce any exported proteases capable of degrading extracellular matrix despite the fact that it is able to disseminate from a skin insertion site to infect multiple organs. Prior studies have shown that B. burgdorferi induces the host protease, matrix metalloproteinase 9 (MMP-9), and suggested that the induction of MMP-9 may allow the organism to disseminate and produce local tissue destruction. We examined the role of MMP-9 in dissemination of B. burgdorferi and pathogenesis of Lyme arthritis. In a MMP-9−/− mouse model, MMP-9 was not required for the dissemination of the spirochete to distant sites. However, MMP-9−/− exhibited significantly decreased arthritis compared to wild-type mice. The decrease in arthritis was not due to an inability to control infection since the spirochete numbers in the joints were identical. Levels of inflammatory chemokines and cytokines were also similar in MMP-9−/− and wild-type mice. We examined whether decreased inflammation in MMP-9−/− mice may be the result of decreased production of neoattractants by MMP-9-dependent cleavage of collagen. MMP-9 cleavage of type I collagen results in increased monocyte chemoattraction. MMP-9 plays an important role in regulating inflammation in Lyme arthritis, potentially through the cleavage of type I collagen.


Stroke ◽  
2006 ◽  
Vol 37 (7) ◽  
pp. 1731-1736 ◽  
Author(s):  
Kirsten B. Holven ◽  
Bente Halvorsen ◽  
Vigdis Bjerkeli ◽  
Jan Kristian Damås ◽  
Kjetil Retterstøl ◽  
...  

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