scholarly journals The Role of PPARs in the Endothelium: Implications for Cancer Therapy

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
David Bishop-Bailey ◽  
Karen E. Swales
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Platelet Activation ◽  
Inflammatory Cell ◽  
Cell Layer ◽  
Cell Recruitment ◽  
Blood Vessel Formation ◽  
Endothelial Cell Layer ◽  
Inflammatory Cell Recruitment

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.

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

2010 ◽  
Vol 89 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Kiminori Kimura ◽  
Satoshi Sekiguchi ◽  
Seishu Hayashi ◽  
Yukiko Hayashi ◽  
Tsunekazu Hishima ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Cell ◽  
Acute Liver Injury ◽  
Interleukin 18 ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

scholarly journals TRAF5 Deficiency Accelerates Atherogenesis in Mice by Increasing Inflammatory Cell Recruitment and Foam Cell Formation

2010 ◽  
Vol 107 (6) ◽  
pp. 757-766 ◽  
Author(s):  
Anna Missiou ◽  
Philipp Rudolf ◽  
Peter Stachon ◽  
Dennis Wolf ◽  
Nerea Varo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cell ◽  
Foam Cell ◽  
Interleukin 1 ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
High Cholesterol Diet ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

Rationale: Tumor necrosis factor receptor–associated factors (TRAFs) are cytoplasmic adaptor proteins for the TNF/interleukin-1/Toll-like receptor superfamily. Ligands of this family comprise multiple important cytokines such as TNFα, CD40L, and interleukin-1β that promote chronic inflammatory diseases such as atherosclerosis. We recently reported overexpression of TRAF5 in murine and human atheromata and that TRAF5 promotes inflammatory functions of cultured endothelial cells and macrophages. Objective: This study tested the hypothesis that TRAF5 modulates atherogenesis in vivo. Methods and Results: Surprisingly, TRAF5 −/− /LDLR −/− mice consuming a high-cholesterol diet for 18 weeks developed significantly larger atherosclerotic lesions than did TRAF5 +/+ /LDLR −/− controls. Plaques of TRAF5-deficient animals contained more lipids and macrophages, whereas smooth muscle cells and collagen remained unchanged. Deficiency of TRAF5 in endothelial cells or in leukocytes enhanced adhesion of inflammatory cells to the endothelium in dynamic adhesion assays in vitro and in murine vessels imaged by intravital microscopy in vivo. TRAF5 deficiency also increased expression of adhesion molecules and chemokines and potentiated macrophage lipid uptake and foam cell formation. These findings coincided with increased activation of JNK and appeared to be independent of TRAF2. Finally, patients with stable or acute coronary heart disease had significantly lower amounts of TRAF5 mRNA in blood compared with healthy controls. Conclusions: Unexpectedly, TRAF5 deficiency accelerates atherogenesis in mice, an effect likely mediated by increased inflammatory cell recruitment to the vessel wall and enhanced foam cell formation.

VEGF and Angiopoietins Promote Inflammatory Cell Recruitment and Mature Blood Vessel Formation in Murine Sponge/Matrigel Model

2014 ◽  
Vol 116 (1) ◽  
pp. 45-57 ◽  
Author(s):  
Tharsika Sinnathamby ◽  
Tae Yun Jin ◽  
Marie-Élaine Clavet-Lanthier ◽  
Cheolho Cheong ◽  
Martin G. Sirois
Keyword(s):  
Blood Vessel ◽  
Inflammatory Cell ◽  
Cell Recruitment ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Inflammatory Cell Recruitment

scholarly journals Expression and Function of the Homeostatic Molecule Del-1 in Endothelial Cells and the Periodontal Tissue

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jieun Shin ◽  
Kavita B. Hosur ◽  
Kalyani Pyaram ◽  
Ravi Jotwani ◽  
Shuang Liang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Inflammatory Cell ◽  
Leukocyte Adhesion ◽  
Neutrophil Infiltration ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression ◽  
Reciprocal Regulation ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein that limits the recruitment of neutrophils by antagonizing the interaction between the LFA-1 integrin on neutrophils and the intercellular adhesion molecule (ICAM)-1 on endothelial cells. Mice with genetic or age-associated Del-1 deficiency exhibit increased neutrophil infiltration in the periodontium resulting in inflammatory bone loss. Here we investigated additional novel mechanisms whereby Del-1 could interfere with neutrophil recruitment and inflammation. Treatment of human endothelial cells with Del-1 did not affect the expression of endothelial molecules involved in the leukocyte adhesion cascade (ICAM-1, VCAM-1, and E-selectin). Moreover, genetic or age-associated Del-1 deficiency did not significantly alter the expression of these adhesion molecules in the murine periodontium, further ruling out altered adhesion molecule expression as a mechanism whereby Del-1 regulates leukocyte recruitment. Strikingly, Del-1 inhibited ICAM-1-dependent chemokine release (CXCL2, CCL3) by neutrophils. Therefore, Del-1 could potentially suppress the amplification of inflammatory cell recruitment mediated through chemokine release by infiltrating neutrophils. Interestingly, Del-1 was itself regulated by inflammatory stimuli, which generally exerted opposite effects on adhesion molecule expression. The reciprocal regulation between Del-1 and inflammation may contribute to optimally balance the protective and the potentially harmful effects of inflammatory cell recruitment.

Platelets are a previously unrecognised source of MIF

2013 ◽  
Vol 110 (11) ◽  
pp. 1004-1013 ◽  
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.

Role of chemokines in proteinuric kidney disorders

2014 ◽  
Vol 16 ◽  
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.

scholarly journals Lung endothelial cell platelet-activating factor production and inflammatory cell adherence are increased in response to cigarette smoke component exposure

2012 ◽  
Vol 302 (1) ◽  
pp. L47-L55 ◽  
Author(s):  
Janhavi Sharma ◽  
Dawn M. Young ◽  
John O. Marentette ◽  
Prerna Rastogi ◽  
John Turk ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Platelet Activating Factor ◽  
Small Airways ◽  
Cell Adherence ◽  
Cell Recruitment ◽  
Raw 264.7 Cell ◽  
Inflammatory Cell Recruitment ◽  
Lung Endothelial Cells

An early event in the pathogenesis of emphysema is the development of inflammation associated with accumulation of polymorphonuclear leukocytes (PMN) in small airways, and inflammatory cell recruitment from the circulation involves migration across endothelial and epithelial cell barriers. Platelet-activating factor (PAF) promotes transendothelial migration in several vascular beds, and we postulated that increased PAF production in the airways of smokers might enhance inflammatory cell recruitment and exacerbate inflammation. To examine this possibility, we incubated human lung microvascular endothelial cells (HMVEC-L) with cigarette smoke extract (CSE) and found that CSE inhibits PAF-acetylhydrolase (PAF-AH) activity. This enhances HMVEC-L PAF production and PMN adherence, and adherence is blocked by PAF receptor antagonists (CV3988 or ginkgolide B). CSE also inhibited PAF-AH activity of lung endothelial cells isolated from wild-type (WT) and iPLA2β knockout mice, and with WT cells, CSE enhanced PAF production and RAW 264.7 cell adherence. In contrast, CSE did not affect PAF production or RAW 264.7 cell adherence to iPLA2β-null cells, suggesting that iPLA2β plays an important role in PAF production by lung endothelial cells. These findings suggest that inhibition of PAF-AH by components of cigarette smoke may initiate or exacerbate inflammatory lung disease by enhancing PAF production and promoting accumulation of inflammatory cells in small airways. In addition, iPLA2β is identified as a potential target for therapeutic interventions to reduce airway inflammation and the progression of chronic lung disease.

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