Platelet‐activating factor induces matrix metalloproteinase‐9 expression through Ca<sup>2+</sup>‐ or PI3K‐dependent signaling pathway in a human vascular endothelial cell line

Ko, Hyun-Mi; Kang, Ji-Hyoun; Choi, Jung-Hwa; Park, Sung Jun; Bai, Suk; Im, Suhn-Young

doi:10.1016/j.febslet.2005.10.027

Cited by 31 publications

(29 citation statements)

References 45 publications

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“…In fact, previous studies have shown the expression of MMP-9 is under the control of a 2.2-kb upstream regulatory region harboring binding sites for AP-1, Ets2, NF-B, and Sp1, some of which are activated during KSHV infection (19,47,48). In endothelial cells, the expression of MMP-9 is regulated by multiple signaling pathways, such as the phosphatidylinositol 3-kinase pathway (25,39). Further studies are required to define the mechanism by which KSHV regulates the expression and secretion of MMP-9.…”

Section: Discussionmentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

Qian

Xie

et al. 2007

J Virol

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Matrix metalloproteinases (MMPs) play important roles in cancer invasion, angiogenesis, and inflammatory infiltration. Kaposi's sarcoma is a highly disseminated angiogenic tumor of proliferative endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we showed that KSHV infection increased the invasiveness of primary human umbilical vein endothelial cells (HUVEC) in a Matrigelbased cell invasion assay. KSHV-induced cell invasion was abolished by an inhibitor of MMPs, BB-94, and occurred in both autocrine-and paracrine-dependent fashions. Analysis by zymography and Western blotting showed that KSHV-infected HUVEC cultures had increased secretion of MMP-1, -2, and -9. KSHV increased the secretion of MMP-2 within 1 h following infection without upregulating its mRNA expression level. In contrast, the secretion of MMP-1 and -9 was not increased until 6 h after KSHV infection and was correlated with the upregulation of their mRNA expression levels. Promoter analysis by reporter assays and electrophoretic mobility shift assays identified an AP-1 cis-element as the dominant KSHV-responsive site in the MMP-1 promoter. Together, these results suggest that KSHV infection modulates the production of multiple MMPs to increase cell invasiveness and thus contributes to the pathogenesis of KSHV-induced malignancies.

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Section: Discussionmentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

Qian

Xie

et al. 2007

J Virol

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“…MMP9 is present in low quantities in the healthy adult lung but much more abundant in COPD, and the inappropriate expression of MMP9 is thought to contribute to the pathogenesis of COPD . MMP9 expression, whether stimulated by PAF or fibronectin, probably through an action on NF-B, is also regulated by PI3K signaling pathways (Ko et al, 2005). Furthermore, several lines of evidence point to the importance of PI3K in the activation of macrophage and neutrophils, which are key players in COPD inflammation (Thomas et al, 2005).…”

Section: Pi3k In Airway Inflammationmentioning

confidence: 99%

Therapeutic Potential of Phosphatidylinositol 3-Kinase Inhibitors in Inflammatory Respiratory Disease

Ito¹,

Caramori²,

Adcock³

2006

J Pharmacol Exp Ther

147

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The phosphoinositide 3-kinase(s) (PI3K) are a family of proteins that catalyze the phosphorylation of the 3-OH position of phosphoinositides and generate lipids that control a wide variety of intracellular signaling pathways. They are classified into three families according to their structure and substrate specificity and are thought to have distinct biological roles. Recent studies suggested that numerous components of the PI3K pathway play a crucial role in the expression and activation of inflammatory mediators, inflammatory cell recruitment, immune cell function, airway remodeling, and corticosteroid insensitivity in chronic inflammatory respiratory disease. Selective PI3K inhibitors have been developed that reduce inflammation and some characteristics of disease in experimental animal models. Targeting specific PI3K isoforms that may be overexpressed or overactive in disease should allow for selective treatment of respiratory diseases. Encouraging data from animal models, primary cells and clinical studies in other diseases suggest that inhibitors of PI3K/Akt may prove to be useful novel therapies in the treatment of asthma and chronic obstructive pulmonary disease.Chronic inflammatory airway diseases, such as bronchial asthma and chronic obstructive pulmonary disease (COPD), represent a profound and growing public health problem worldwide. Bronchial asthma, in addition to placing a considerable burden in terms of direct medical costs, has enormous indirect costs and is one of the leading causes of work or school absenteeism. Most patients with asthma respond well to current corticosteroid-based therapies; however, a small percentage (10%) fails to respond well and this poor control of symptoms is a major issue that can result in adverse clinical and economic outcomes (accounting for Ͼ50% of the total asthma health care costs). COPD (smoking lung) is a chronic inflammatory disease of the lower airways and lung, and this progressive and relentless loss of lung function is caused by emphysema due to destruction of lung parenchyma and by narrowing of small airways as a result of chronic inflammation Barnes and Kleinert, 2004). COPD is predicted to become the third most common cause of death and the fifth most common cause of disability in the world by 2020 (Barnes and Kleinert, 2004). Cystic fibrosis is also recognized as an inflammatory disease with increased neutrophilia, inflammatory gene expression, and enhanced activation of several transcription factors. Unfortunately, there are no effective treatments for these diseases (severe asthma and COPD and cystic fibrosis), and the molecular mechanisms underlying their pathogenesis are not fully understood. Recent research suggests that many kinases are involved in chronic airway inflammation and its This research is funded by The Wellcome Trust (UK), The Medical Research Council (UK), Associazione per la Ricerca e la Cura dell'Asma (ARCA, Padova, Italy), Chiesi Farmaceutici (Italy), GlaxoSmithKline (UK), AstraZeneca, Mitsubishi (Japan), and Pfizer (U.S...

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“…It is known that the ERK1/ 2 pathway is necessary for MMP-9 induction by homocysteine, (37) α3β1 integrin (38) and ras oncogene, (39) and that MMP-9 induction by platelet-activating factor iss dependent on PI3K. (40) Integrin signals are thought to stimulate focal adhesion kinase, a tyrosine kinase that leads to activation of PI3K, (41,42) and the PI3K/Akt pathway modulates mitochondrial functions. (43) The results shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Induction of matrix metalloproteinase gene expression in an endothelial cell line by direct interaction with malignant cells

et al. 2006

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Mouse endothelial TKD2 cells in monolayers were cocultured with various human cell lines for 24 h, and the expression of several secreted matrix metalloproteinases (MMP) and cell adhesion molecules was examined by real-time reverse transcription-polymerase chain reaction using mouse-specific primers. Coculture with normal fibroblasts did not elicit the expression of these molecules, but coculture with cancer cells induced the expression of MMP-3, MMP-9 and MMP-10 mRNA in endothelial cells, and in normal mouse embryonic fibroblasts. The induction of MMP mRNA was dependent on direct cell adhesion, as separate culture of A549 cells in Boyden chambers did not induce MMP mRNA, and neutralizing antibody against VLA-4 abolished the induction. An inhibitor of phosphatidylinositol-3-phosphate kinase strongly suppressed the induction of MMP-3, MMP-9 and MMP-10 mRNA, and expression of the dominant-negative mutant of phosphatidylinositol-3-phosphate kinase also decreased the induction. It was suggested that intracellular reactive oxygen species (ROS) levels were increased in TKD2 cells following adhesion to cancer cells. ROS scavengers decreased the levels of MMP induction, and roterone, an inhibitor of mitochondrial complex I, strongly suppressed the induction of MMP-3, MMP-9 and MMP-10. The depletion of mitochondria in TKD2 cells decreased the induction of MMP-9, but the induction of MMP-3 and MMP-10 was not affected. These results indicate that the adhesion of cancer cells to endothelial cells activates several distinct signaling pathways to induce MMP gene expression, and the pathways for MMP-3, MMP-9 and MMP-10 are partly different. For the induction of MMP-9, mitochondria participate in induction, possibly through the production of ROS.

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Platelet‐activating factor induces matrix metalloproteinase‐9 expression through Ca²⁺‐ or PI3K‐dependent signaling pathway in a human vascular endothelial cell line

Cited by 31 publications

References 45 publications

Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

Therapeutic Potential of Phosphatidylinositol 3-Kinase Inhibitors in Inflammatory Respiratory Disease

Induction of matrix metalloproteinase gene expression in an endothelial cell line by direct interaction with malignant cells

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Platelet‐activating factor induces matrix metalloproteinase‐9 expression through Ca2+‐ or PI3K‐dependent signaling pathway in a human vascular endothelial cell line

Cited by 31 publications

References 45 publications

Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

Therapeutic Potential of Phosphatidylinositol 3-Kinase Inhibitors in Inflammatory Respiratory Disease

Induction of matrix metalloproteinase gene expression in an endothelial cell line by direct interaction with malignant cells

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Platelet‐activating factor induces matrix metalloproteinase‐9 expression through Ca²⁺‐ or PI3K‐dependent signaling pathway in a human vascular endothelial cell line