Van Lint, P. & Libert, C. Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J. Leukocyte Biol. 82, 1375-1381

Department of Molecular Biomedical Research, Ghent University, Ghent, Belgium.
Journal of Leukocyte Biology (Impact Factor: 4.29). 01/2008; 82(6):1375-81. DOI: 10.1189/jlb.0607338
Source: PubMed


The action of matrix metalloproteinases (MMPs) was originally believed to be restricted to degradation of the extracellular matrix; however, in recent years, it has become evident that these proteases can modify many nonmatrix substrates, such as cytokines and chemokines. The use of MMP-deficient animals has revealed that these proteases can indeed influence the progression of various inflammatory processes. This review aims to provide the reader with a concise overview of these novel MMP functions in relation to leukocyte migration.

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Available from: Philippe Van Lint, May 04, 2015
    • "UV irradiation induces the expression of MMPs and triggers cleavage of cell-surface receptors and protein kinase signal transduction pathways and activation of transcription factors (Fisher et al., 2002). MMPs degrade all kinds of extracellular matrix proteins and damage connective tissues (Kahari and Saarialho- Kere, 1997) and induce the release of cytokines and chemokines and cleave cell surface receptors (Van and Libert, 2007). They also play a role in tissue remodeling and disease processes such as arthritis (Burrage et al., 2006). "
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    ABSTRACT: Ultraviolet (UV) irradiation from the sun is the primary environmental factor that causes human skin aging. UV irradiation induces the expressions of matrix metalloproteinases (MMPs) and extracellular matrix degrading enzymes. Among the members of MMP family, MMP-1 is an interstitial collagenase that degrades the collagen triple helix. We investigated the effect of Lactobacillus plantarum, well known as useful microorganism, on UV-induced-MMP-1 expression in human dermal fibroblasts. Human dermal fibroblasts (HDF) was pre-stimulated with lipoteichoic acid isolated from L. plantarum followed by UV irradiation. Secreted protein level of MMP-1 was evaluated by Western blot analysis. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) from the cell lysates was also examined by western blotting. Electrophoretic mobility-shift assay (EMSA) was used to detect the activated transcription factor, AP-1 and NF-κB. The detection of type 1 procollagen was carried with Procollagen type 1 C-peptide (PIP) EIA kit. The generation of reactive oxygen species (ROS) by LTA and UV irradiation was examined by Griess reagent assay and fluorescence microscope. We found that lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, isolated from L. plantarum, inhibited MMP-1 expression. Pretreatment with LTA from L. plantarum (pLTA) reduced MMP-1 expression in a dose-dependent manner and inhibited activation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK). It also led to the inhibition of DNA binding activity of activator protein-1 (AP-1) and of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB). Furthermore, LTA promoted type 1 procollagen synthesis and reduced the generation of ROS induced by UV irradiation. Our study demonstrates that pLTA inhibits degradation of collagen and promotes its synthesis and that pLTA contributes to a decrease in ROS production. Therefore, pLTA from L. plantarum has potential abilities to prevent and treat skin photo-aging. Copyright © 2015. Published by Elsevier Ltd.
    Molecular Immunology 06/2015; 67(2 Pt B). DOI:10.1016/j.molimm.2015.05.019 · 2.97 Impact Factor
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    • "MMPs aid in establishing a chemotactic signal for recruitment of leukocytes and at the same time degrade ECM and junctional proteins, promoting leukocyte infiltration. Chemokines are immobilized mostly on the ECM or cell surface by binding to glycosaminoglycans and MMPs might contribute to the liberation of these molecules, delivering soluble effectors in the extracellular environment [8]. Paracellular movement of leukocytes is impeded by tight junctions and adherens junctions that occlude the intercellular cleft. "
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    ABSTRACT: The coordination of tissue function is mediated by gap junctions (GJs) that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx) proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs) in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs) are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.
    Mediators of Inflammation 01/2015; 2015(2):1-18. DOI:10.1155/2015/257471 · 3.24 Impact Factor
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    • "e l s e v i e r . c o m / l o c a t e / y b b r c induce cytoskeletal rearrangement and induce the cellular adhesion of neoplastic cells as well as their migration [13]. It has been well documented in literature that upregulation cellular inflammatory adhesion through chemokine–ligand, CXCL12–CXCR4, interactions play a critical role in the metastasis of breast cancer to lungs and lymph nodes [14]. "
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    ABSTRACT: Matrix metalloproteinases (MMP-2 and -9) play an important role in the tumor metastasis through cleavage of proinflammatory cytokines. Violacein a small molecule produced by Chromobacterium violaceum and has been implicated with anti-cancer effects. In this study we investigated the molecular basis of violacein mediated downregulation of CXCL12/CXCR4, chemokine-receptor ligand interaction. Zymography analysis demonstrated that violacein significantly inhibited the cytokine (TNF alpha and TGF beta) mediated MMP-2 activation in MCF-7 breast cancer cell line. MMP-2 plays a critical role in the secretion of inflammatory chemokine, CXCL12, involved in cell migration and cancer metastasis. ELISA analysis demonstrated that violacein inhibited the secretion of CXCL12 from the activated MCF-7 cells. Further, we show that MMP-2/-9 act synergistically at two distinct steps towards the membrane expression of the tumor metastasis chemokine receptor, CXCR4. Violacein efficiently downregulated the CXCR4 membrane expression through MMP-9 inhibition. Taken together, these studies demonstrate a unique anti-tumor mechanism of action of violacein through reduction of CXCL12/CXCR4 interaction. These studies could offer a novel venue for violacein in cancer therapy.
    Biochemical and Biophysical Research Communications 10/2014; 455(1-2). DOI:10.1016/j.bbrc.2014.10.124 · 2.30 Impact Factor
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