scholarly journals Cyanobacteria Scytonema javanicum and Scytonema ocellatum Lipopolysaccharides Elicit Release of Superoxide Anion, Matrix-metalloproteinase-9, Cytokines and Chemokines by Rat Microglia In Vitro

2018 ◽  
Author(s):  
Lucas C. Klemm ◽  
Evan Czerwonka ◽  
Mary L. Hall ◽  
Philip G. Williams ◽  
Alejandro M.S. Mayer
Keyword(s):  
Matrix Metalloproteinase ◽  
Superoxide Anion ◽  
Matrix Metalloproteinase 9 ◽  
Alternative Activation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
E Coli ◽  
Cytokines And Chemokines ◽  
Metalloproteinase 9

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. 

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.

Interferon β-1b decreases the migration of T lymphocytes in vitro: Effects on matrix metalloproteinase-9

1996 ◽  
Vol 40 (6) ◽  
pp. 853-863 ◽  
Author(s):  
Olaf Stüve ◽  
Nora P. Dooley ◽  
Joon H. Uhm ◽  
Jack P. Antel ◽  
Gordon S. Francis ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 9 ◽  
Interferon Β ◽  
In Vitro Effects ◽  
Metalloproteinase 9

scholarly journals 617. Efficacy of Dimercaptosuccinic Acid (DMSA), a Zinc Chelator, in Combination with Imipenem Against Metallo-β-Lactamase Producing Escherichia coli in a Murine Peritonitis Model

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S287-S287
Author(s):  
Geoffrey Cheminet ◽  
Patrice Nordmann ◽  
Francoise Chau ◽  
Nicolas Kieffer ◽  
Katell Peoc’h ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Concentration Dependent Manner ◽  
Bacterial Counts ◽  
E Coli ◽  
Zinc Chelator ◽  
Peritonitis Model

Abstract Background A strategy used by bacterial strains to resist β-lactam antibiotics is the expression of metallo-β-lactamases (MBL) requiring zinc for activity. The use of a zinc chelator may restore carbapenem activity against MBL-producing Enterobacteriaceae. DMSA is a heavy metal chelator approved in humans with a satisfactory safety record. Our objective was to evaluate the activity of DMSA in combination with carbapenems, in vitro and in a fatal murine peritonitis model, against MBL-producing Escherichia coli. Methods Isogenic derivatives of wild-type E. coli CFT073 producing the MBL NDM-1, VIM-2, IMP-1, and the serine carbapenemases OXA-48 and KPC-3 were constructed. Minimum inhibitory concentrations (MICs) of imipenem, meropenem, and ertapenem were determined against each strain alone or in combination with DMSA. Mice were infected with E. coli CFT073 or NDM-1 and treated intraperitoneally for 24 hours with imipenem 100 mg/kg every 4 hours, DMSA 200 mg/kg every 4 hours, or both. Mice survival rates and bacterial counts in peritoneal fluid (PF) and spleen were assessed at 24 hours. Results In vitro, DMSA in combination with each carbapenem permitted a significant decrease of the MICs against all MBL-producing strains, in a concentration-dependent manner. The maximum effect was found for the NDM-1 strain with a 6- to 8-fold MIC reduction, depending on the carbapenem used. NDM-1 strain became susceptible to carbapenems with concentrations of DMSA ≥6 mM. Increasing zinc concentrations above 1 mg/L (average human plasma concentration) did not alter this effect. No benefit of DMSA was observed against non-MBL strains. In vivo, when used alone, the DMSA regimen was not toxic in uninfected mice and ineffective against NDM-1-infected mice (100% mortality). Combination of imipenem and DMSA significantly reduced bacterial counts in PF and spleen as compared with imipenem alone (P < 0.001), and reduced mortality, although not significantly (11% vs. 37%, respectively, P = 0.12). No benefit of the combination was observed against CFT073. Conclusion DMSA is highly effective in vitro in reducing carbapenems MICs against MBL-producing E. coli and appears as a promising strategy in combination with carbapenems for the treatment of NDM-1-related infections. Disclosures All authors: No reported disclosures.

scholarly journals Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9

2013 ◽  
Vol 304 (12) ◽  
pp. E1365-E1378 ◽  
Author(s):  
Sourav Kundu ◽  
Sathnur B. Pushpakumar ◽  
Aaron Tyagi ◽  
Denise Coley ◽  
Utpal Sen
Keyword(s):  
Hydrogen Sulfide ◽  
Matrix Metalloproteinase ◽  
Therapeutic Potential ◽  
Matrix Metalloproteinase 9 ◽  
Double Knockout ◽  
Diabetic Kidney ◽  
Connexin 40 ◽  
Akita Mice ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) causes adverse remodeling, whereas hydrogen sulfide (H2S) rescues organs in vascular diseases. The involvement of MMP-9 and H2S in diabetic renovascular remodeling is, however, not well characterized. We determined whether MMP-9 regulates H2S generation and whether H2S modulates connexin through N-methyl-d-aspartate receptor (NMDA-R)-mediated pathway in the diabetic kidney. Wild-type (WT, C57BL/6J), diabetic (Akita, C57BL/6J- Ins2 Akita), MMP-9−/− (M9KO), double knockout (DKO) of Akita/MMP-9−/− mice and in vitro cell culture were used in our study. Hyperglycemic Akita mice exhibited increased level of MMP-9 and decreased production of H2S. H2S-synthesizing enzymes cystathionine-β-synthase and cystathionine-γ-lyase were also diminished. In addition, increased expressions of NMDA-R1 and connexin-40 and -43 were observed in diabetic kidney. As expected, MMP-9 mRNA was not detected in M9KO kidneys. However, very thin protein expression and activity were detected. No other changes were noticed in M9KO kidney. In DKO mice, all the above molecules showed a trend toward baseline despite hyperglycemia. In vitro, glomerular endothelial cells treated with high glucose showed induction of MMP-9, attenuated H2S production, NMDA-R1 induction, and dysregulated conexin-40 and -43 expressions. Silencing MMP-9 by siRNA or inhibition of NMDA-R1 by MK801 or H2S treatment preserved connexin-40 and -43. We conclude that in diabetic renovascular remodeling MMP-9 plays a major role and that H2S has therapeutic potential to prevent adverse diabetic renal remodeling.

scholarly journals Secretion of matrix metalloproteinase-9 by macrophages,in vitro, in response toHelicobacter pylori

2005 ◽  
Vol 45 (2) ◽  
pp. 159-169 ◽  
Author(s):  
Bergin Philip James ◽  
Wen Sicheng ◽  
Pan-Hammarström Qiang ◽  
Quiding-Järbrink Marianne
Keyword(s):  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9
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