Thymoquinone from nutraceutical black cumin oil activates Neu4 sialidase in live macrophage, dendritic, and normal and type I sialidosis human fibroblast cells via GPCR Gαi proteins and matrix metalloproteinase-9

Matrix metalloproteinase-9 (MMP-9) is a matrix-degrading enzyme implicated in many biological processes, including inflammation. It is produced by many cells, including fibroblasts. When cultured in three-dimensional (3D) collagen gels, fibroblasts contract the surrounding matrix, a function that is thought to model the contraction that characterizes both normal wound repair and fibrosis. The current study was designed to evaluate the role of endogenously produced MMP-9 in fibroblast contraction of 3D collagen gels. Fibroblasts from mice lacking expression of MMP-9 and human lung fibroblasts (HFL-1) transfected with MMP-9 small-interfering RNA (siRNA) were used. Fibroblasts were cast into type I collagen gels and floated in culture medium with or without transforming growth factor (TGF)-β1 for 5 days. Gel size was determined daily using an image analysis system. Gels made from MMP-9 siRNA-treated human fibroblasts contracted less than control fibroblasts, as did fibroblasts incubated with a nonspecific MMP inhibitor. Similarly, fibroblasts cultured from MMP-9-deficient mice contracted gels less than did fibroblasts from control mice. Transfection of the MMP-9-deficient murine fibroblasts with a vector expressing murine MMP-9 restored contractile activity to MMP-9-deficient fibroblasts. Inhibition of MMP-9 reduced active TGF-β1 and reduced several TGF-β1-driven responses, including activity of a Smad3 reporter gene and production of fibronectin. Because TGF-β1 also drives fibroblast gel contraction, this suggests the mechanism for MMP-9 regulation of contraction is through the generation of active TGF-β1. This study provides direct evidence that endogenously produced MMP-9 has a role in regulation of tissue contraction of 3D collagen gels mediated by fibroblasts.

Download Full-text

Leukocyte matrix metalloproteinase-9 is elevated and contributes to lymphocyte activation in type I diabetes

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2005.06.003 ◽

2005 ◽

Vol 37 (11) ◽

pp. 2406-2416 ◽

Cited By ~ 15

Author(s):

Meilang Xue ◽

Patrick J. Thompson ◽

Rory Clifton-Bligh ◽

Greg Fulcher ◽

Eileen D.M. Gallery ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Type I Diabetes ◽

Lymphocyte Activation ◽

Matrix Metalloproteinase 9 ◽

Type I ◽

Metalloproteinase 9

Download Full-text

Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination of Borrelia burgdorferi

Infection and Immunity ◽

10.1128/iai.00214-09 ◽

2009 ◽

Vol 77 (7) ◽

pp. 2643-2649 ◽

Cited By ~ 30

Author(s):

Andrew J. Heilpern ◽

Warren Wertheim ◽

Jia He ◽

George Perides ◽

Roderick T. Bronson ◽

...

Keyword(s):

Borrelia Burgdorferi ◽

Matrix Metalloproteinase ◽

Type I Collagen ◽

Insertion Site ◽

Matrix Metalloproteinase 9 ◽

Lyme Arthritis ◽

Type I ◽

Wild Type ◽

Tissue Destruction ◽

Metalloproteinase 9

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.

Download Full-text

Inhibition of ornithine decarboxylase in human fibroblast cells by type I and type II interferons

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(83)90652-6 ◽

1983 ◽

Vol 114 (3) ◽

pp. 950-954 ◽

Cited By ~ 34

Author(s):

Vaithilingam Sekar ◽

Valerie J. Atmar ◽

Arati R. Joshi ◽

Mathilde Krim ◽

Glenn D. Kuehn

Keyword(s):

Ornithine Decarboxylase ◽

Human Fibroblast ◽

Type I ◽

Fibroblast Cells ◽

Type Ii ◽

Human Fibroblast Cells

Download Full-text

Matrix Metalloproteinase 9 Facilitates Hepatitis B Virus Replication through Binding with Type I Interferon (IFN) Receptor 1 To Repress IFN/JAK/STAT Signaling

Journal of Virology ◽

10.1128/jvi.01824-16 ◽

2017 ◽

Vol 91 (8) ◽

Cited By ~ 26

Author(s):

Junbo Chen ◽

Wei Xu ◽

Yanni Chen ◽

Xueping Xie ◽

Yecheng Zhang ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Matrix Metalloproteinase ◽

Chronic Infection ◽

Matrix Metalloproteinase 9 ◽

Host Immunity ◽

Type I ◽

Hbv Replication ◽

B Virus ◽

Metalloproteinase 9

ABSTRACT Hepatitis B virus (HBV) infection may cause acute hepatitis B, chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV evades host immunity and maintains chronic infection are largely unknown. Here, we revealed that matrix metalloproteinase 9 (MMP-9) is activated in peripheral blood mononuclear cells (PBMCs) of HBV-infected patients, and HBV stimulates MMP-9 expression in macrophages and PBMCs isolated from healthy individuals. MMP-9 plays important roles in the breakdown of the extracellular matrix and in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. MMP-9 also regulates respiratory syncytial virus (RSV) replication, but the mechanism underlying such regulation is unknown. We further demonstrated that MMP-9 facilitates HBV replication by repressing the interferon (IFN)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, IFN action, STAT1/2 phosphorylation, and IFN-stimulated gene (ISG) expression. Moreover, MMP-9 binds to type I IFN receptor 1 (IFNAR1) and facilitates IFNAR1 phosphorylation, ubiquitination, subcellular distribution, and degradation to interfere with the binding of IFANR1 to IFN-α. Thus, we identified a novel positive-feedback regulation loop between HBV replication and MMP-9 production. On one hand, HBV activates MMP-9 in infected patients and leukocytes. On the other hand, MMP-9 facilitates HBV replication through repressing IFN/JAK/STAT signaling, IFNAR1 function, and IFN-α action. Therefore, HBV may take the advantage of MMP-9 function to establish or maintain chronic infection. IMPORTANCE Hepatitis B virus (HBV) infection may cause chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV maintains chronic infection are largely unknown. Matrix metalloproteinase 9 (MMP-9) plays important roles in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. However, the effects of MMP-9 on HBV replication and pathogenesis are not known. This study reveals that MMP-9 expression is activated in patients with CHB, and HBV stimulates MMP-9 production in PBMCs and macrophages. More interestingly, MMP-9 in turn promotes HBV replication through suppressing IFN-α action. Moreover, MMP-9 interacts with type I interferon receptor 1 (IFNAR1) to disturb the binding of IFN-α to IFNAR1 and facilitate the phosphorylation, ubiquitination, subcellular distribution, and degradation of IFNAR1. Therefore, these results discover a novel role of MMP-9 in viral replication and reveal a new mechanism by which HBV evades host immunity to maintain persistent infection.

Download Full-text

Regulation of matrix metalloproteinase-9 expression between gingival fibroblast cells from old and young rats

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2008.09.015 ◽

2009 ◽

Vol 378 (2) ◽

pp. 152-156 ◽

Cited By ~ 7

Author(s):

Su-Jung Kim ◽

Yong-Koo Chung ◽

Tae-Wook Chung ◽

Jeong-Ran Kim ◽

Sung-Kwon Moon ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Gingival Fibroblast ◽

Fibroblast Cells ◽

Young Rats ◽

Metalloproteinase 9

Download Full-text

Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats

PLoS ONE ◽

10.1371/journal.pone.0244650 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0244650

Author(s):

Maha Sabry ◽

Seham Mostafa ◽

Laila Rashed ◽

Marwa Abdelgwad ◽

Samaa Kamar ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

High Fat Diet ◽

Inflammatory Markers ◽

Type I Collagen ◽

Bone Diseases ◽

Matrix Metalloproteinase 9 ◽

Type I ◽

High Fat ◽

Major Player ◽

Metalloproteinase 9

Background Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. On the other hand, the relationship between bone diseases and obesity remains unclear. An increasing number of biological and epidemiological studies suggest the presence of a link between atherosclerosis and osteoporosis, however, the precise molecular pathways underlying this close association remain poorly understood. The present work thus aimed to study Matrix Metalloproteinase 9 (MMP-9), as a proposed link between atherosclerosis and osteoporosis in high fat diet fed rats. Methods and findings 40 rats were randomly divided into 4 groups: control, untreated atherosclerosis group, atherosclerotic rats treated with carvedilol (10mg/kg/d) and atherosclerotic rats treated with alendronate sodium (10mg/kg/d). After 8 weeks, blood samples were collected for estimation of Lipid profile (Total cholesterol, HDL, TGs), inflammatory markers (IL-6, TNF-α, CRP and NO) and Bone turnover markers (BTMs) (Alkaline phosphatase, osteocalcin and pyridinoline). Rats were then euthanized and the aortas and tibias were dissected for histological examination and estimation of MMP-9, N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX) and NF-kB expression. Induction of atherosclerosis via high fat diet and chronic stress induced a significant increase in BTMs, inflammatory markers and resulted in a state of dyslipidaemia. MMP-9 has also shown to be significantly increased in the untreated atherosclerosis rats and showed a significant correlation with all measured parameters. Interestingly, Carvedilol and bisphosphonate had almost equal effects restoring the measured parameters back to normal, partially or completely. Conclusion MMP-9 is a pivotal molecule that impact the atherogenic environment of the vessel wall. A strong cross talk exists between MMP-9, cytokine production and macrophage function. It also plays an important regulatory role in osteoclastogenesis. So, it may be a key molecule in charge for coupling CVD and bone diseases in high fat diet fed rats. Therefore, we suggest MMP-9 as a worthy molecule to be targeted pharmacologically in order to control both conditions simultaneously. Further studies are needed to support, to invest and to translate this hypothesis into clinical studies and guidelines.

Download Full-text