Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury

The growth and metastasis of cancers intimately involve the vasculature and in particular the endothelial cell layer. Tumours require new blood vessel formation via angiogenesis to support growth. In addition, inflammation, coagulation, and platelet activation are common signals in the growth and metastasis of tumour cells. The endothelium plays a central role in the homeostatic control of inflammatory cell recruitment, regulating platelet activation and coagulation pathways. PPAR, -/, and - are all expressed in endothelial cells. This review will discuss the roles of PPARs in endothelial cells in relation to angiogenesis, inflammation, coagulation, and platelet control pathways. In particular, we will discuss the recent evidence that supports the hypothesis that PPAR and PPAR are antiangiogenic receptors, while PPAR/ is proangiogenic.

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Platelets are a previously unrecognised source of MIF

Thrombosis and Haemostasis ◽

10.1160/th13-01-0049 ◽

2013 ◽

Vol 110 (11) ◽

pp. 1004-1013 ◽

Cited By ~ 34

Author(s):

Theresa Wirtz ◽

Richard Bucala ◽

Philipp von Hundelshausen ◽

Tim Strüßmann ◽

Sabine Tillmann ◽

...

Keyword(s):

Inflammatory Cell ◽

Subcellular Localisation ◽

Cell Recruitment ◽

Activated Platelets ◽

Inflammatory Processes ◽

Monocyte Chemotaxis ◽

Inflammatory Cell Recruitment ◽

Low Levels ◽

Human And Mouse

SummaryMacrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions and a role in atherogenesis. MIF is secreted by various cells including endothelial cells and macrophages. Platelets are another prominent cell type with a role in atherogenesis and are a rich source of atherogenic chemokines. We asked whether platelets express and secrete MIF. In comparison, CXCL12 release was determined. We examined the subcellular localisation of MIF in platelets/ megakaryocytes, studied its co-localisation with other plateletderived mediators and asked whether platelets contain MIF mRNA. Moreover, we probed the functional role of platelet-derived MIF in inflammatory cell recruitment. Using Western blot and ELISA, we demonstrated and quantitated MIF protein in human and mouse platelets. Applying confocal-microscopy, MIF was found to localise in granularlike structures, but did not co-localise with known platelet cytokines. qPCR indicated that platelets contain low levels of MIF mRNA. ELISA measurements from human platelet supernatants showed that, whereas thrombin and collagen triggered the release of MIF and CXCL12, ADP and oxidised LDL promoted CXCL12 but not MIF secretion. Using Transwell assays, we demonstrated that platelet supernatants promoted monocyte chemotaxis and that this was blocked by neutralising MIF antibodies. This is the first report demonstrating MIF secretion from activated platelets, suggesting that platelets are a previously unrecognised source of MIF in inflammatory processes. There are distinct activating stimuli for MIF and CXCL12 secretion. A substantial portion of the chemotactic capacity of stimulated platelet supernatants is contributed by MIF, suggesting a role for platelet-derived MIF in atherogenic cell recruitment.

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Role of chemokines in proteinuric kidney disorders

Expert Reviews in Molecular Medicine ◽

10.1017/erm.2014.3 ◽

2014 ◽

Vol 16 ◽

Cited By ~ 17

Author(s):

Juan Antonio Moreno ◽

Sara Moreno ◽

Alfonso Rubio-Navarro ◽

Carmen Gómez-Guerrero ◽

Alberto Ortiz ◽

...

Keyword(s):

Renal Impairment ◽

Recent Progress ◽

Inflammatory Cell ◽

Therapeutic Potential ◽

Clinical Implications ◽

Tubular Epithelial Cells ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment ◽

Progression Of Renal Disease

Experimental and human studies have shown that proteinuria contributes to the progression of renal disease. Overexposure to filtered proteins promotes the expression and release of chemokines by tubular epithelial cells, thus leading to inflammatory cell recruitment and renal impairment. This review focuses on recent progress in cellular and molecular understanding of the role of chemokines in the pathogenesis of proteinuria-induced renal injury, as well as their clinical implications and therapeutic potential.

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Phosphoinositide 3-kinases and their role in inflammation: potential clinical targets in atherosclerosis?

Clinical Science ◽

10.1042/cs20080549 ◽

2009 ◽

Vol 116 (11) ◽

pp. 791-804 ◽

Cited By ~ 25

Author(s):

Anne Fougerat ◽

Stéphanie Gayral ◽

Nicole Malet ◽

Fabienne Briand-Mesange ◽

Monique Breton-Douillon ◽

...

Keyword(s):

Inflammatory Cell ◽

Signalling Pathways ◽

Cell Recruitment ◽

Intracellular Signalling Pathways ◽

Inflammatory Processes ◽

Inflammatory Proteins ◽

Inflammatory Cell Recruitment ◽

Phosphoinositide 3 Kinase ◽

Innovative Drugs

Inflammation has a central role in the pathogenesis of atherosclerosis at various stages of the disease. Therefore it appears of great interest to develop novel and innovative drugs targeting inflammatory proteins for the treatment of atherosclerosis. The PI3K (phosphoinositide 3-kinase) family, which catalyses the phosphorylation of the 3-OH position of phosphoinositides and generates phospholipids, controls a wide variety of intracellular signalling pathways. Recent studies provide evidence for a crucial role of this family not only in immune function, such as inflammatory cell recruitment, and expression and activation of inflammatory mediators, but also in antigen-dependent responses making it an interesting target to modulate inflammatory processes. The present review will focus on the regulation of inflammation within the vasculature during atherogenesis. We will concentrate on the different functions played by each isoform of PI3K in immune cells which could be involved in this pathology, raising the possibility that inhibition of one or more PI3K isoforms may represent an effective approach in the treatment of atherosclerosis.

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Dynamics of inflammatory cell recruitment in a cigarette smoke induced COPD mouse model

Pneumologie ◽

10.1055/s-0031-1296117 ◽

2011 ◽

Vol 65 (12) ◽

Author(s):

K Kohse ◽

G John ◽

O Eickelberg ◽

AÖ Yildirim

Keyword(s):

Mouse Model ◽

Cigarette Smoke ◽

Inflammatory Cell ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment

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Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

PLoS ONE ◽

10.1371/journal.pone.0145147 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145147 ◽

Cited By ~ 7

Author(s):

Silvia Affò ◽

Daniel Rodrigo-Torres ◽

Delia Blaya ◽

Oriol Morales-Ibanez ◽

Mar Coll ◽

...

Keyword(s):

Chemokine Receptor ◽

Inflammatory Cell ◽

Liver Inflammation ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment

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The role of non-steroidal anti-inflammatory drugs in acute liver injury.

BMJ ◽

10.1136/bmj.305.6858.865 ◽

1992 ◽

Vol 305 (6858) ◽

pp. 865-868 ◽

Cited By ~ 70

Author(s):

L. A. Garcia Rodriguez ◽

S. Perez Gutthann ◽

A. M. Walker ◽

L. Lueck

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Inflammatory Drugs ◽

Anti Inflammatory

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The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01098-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6317-6327 ◽

Cited By ~ 21

Author(s):

Hussein Traboulsi ◽

Alexandre Cloutier ◽

Kumaraswamy Boyapelly ◽

Marc-André Bonin ◽

Éric Marsault ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Inflammatory Response ◽

Lung Inflammation ◽

Inflammatory Cell ◽

Influenza Virus Infection ◽

Cytokine Gene Expression ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment ◽

Anti Inflammatory

ABSTRACTThe host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

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