scholarly journals Monocyte Subsets Coregulate Inflammatory Responses by Integrated Signaling through TNF and IL-6 at the Endothelial Cell Interface

2017 ◽  
Vol 198 (7) ◽  
pp. 2834-2843 ◽  
Author(s):  
Myriam Chimen ◽  
Clara M. Yates ◽  
Helen M. McGettrick ◽  
Lewis S. C. Ward ◽  
Matthew J. Harrison ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Monocyte Subsets ◽  
Cell Interface

Abstract 153: IL-10 Accelerates Re-Endothelialization and Inhibits Post-injury Intimal Hyperplasia following Carotid Artery Denudation by Attenuating TNF-alpha-induced Endothelial Cell Dysfunction

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Suresh K Verma ◽  
Prasanna Krishnamurthy ◽  
Alexander R Mackie ◽  
Erin E Vaughan ◽  
Mohsin Khan ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Thrombus Formation ◽  
Specific Effect ◽  
Mononuclear Phagocytes ◽  
Tnf Alpha ◽  
Post Injury ◽  
Knock Out ◽  
Cytokines And Chemokines

The association of inflammation with atherosclerosis and restenosis is now fairly well established. Restenosis, a persistent complication of percutaneous vascular interventions, is thought to be a complex response to injury, which includes early thrombus formation, neointimal growth and acute inflammation. Mononuclear phagocytes are likely participants in the host response to vascular injury, via the secretion of cytokines and chemokines, including TNF-alpha (TNF). Others and we have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (EC) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL10KO) displayed significantly delayed ReEndothelialization and enhanced neointimal growth compared to their WT counterparts. Exogenous treatment of recombinant IL-10 dramatically blunted the inflammatory cell infiltration and neointimal thickening while significantly accelerating the recovery of the injured endothelium both WT and IL10KO mice. In vitro, IL10 co-treatment reversed TNF-mediated growth arrest, EC cell cycle inhibition, EC-monocyte adhesion and EC apoptosis. At signaling level, IL-10 reduced TNF-induced activation of JNK MAP kinase while simultaneously activating PI3K/Akt pathway. Because IL-10 function and signaling are important components for control of inflammatory responses, these results may provide insights necessary to develop strategies for modulating vascular repair and other accelerated arteriopathies, including transplant vasculopathy and vein graft hyperplasia.

scholarly journals Nitric oxide degradation of heparin and heparan sulphate

1997 ◽  
Vol 324 (2) ◽  
pp. 473-479 ◽  
Author(s):  
Rolando E. VILAR ◽  
Dineshchandra GHAEL ◽  
Min LI ◽  
Devan D. BHAGAT ◽  
Lisa M. ARRIGO ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Molecular Mass ◽  
Inflammatory Responses ◽  
Degradation Products ◽  
Bone Development ◽  
Heparan Sulphate ◽  
Gel Filtration ◽  
No Synthase ◽  
Strong Anion Exchange

NO is a bioactive free radical produced by NO synthase in various tissues including vascular endothelium. One of the degradation products of NO is HNO2, an agent known to degrade heparin and heparan sulphate. This report documents degradation of heparin by cultured endothelial-cell-derived as well as exogenous NO. An exogenous narrow molecular-mass preparation of heparin was recovered from the medium of cultured endothelial cells using strong-anion exchange. In addition, another narrow molecular-mass preparation of heparin was gassed with exogenous NO under argon. Degradation was evaluated by gel-filtration chromatography. Since HNO2 degrades heparin under acidic conditions, the reaction with NO gas was studied under various pH conditions. The results show that the degradation of exogenous heparin by endothelial cells is inhibited by NO synthase inhibitors. Exogenous NO gas at concentrations as low as 400 p.p.m. degrades heparin and heparan sulphate. Exogenous NO degrades heparin at neutral as well as acidic pH. Endothelial-cell-derived NO, as well as exogenous NO gas, did not degrade hyaluronan, an unrelated glycosaminoglycan that resists HNO2 degradation. Peroxynitrite, a metabolic product of the reaction of NO with superoxide, is an agent that degrades hyaluronan; however, peroxynitrite did not degrade heparin. Thus endothelial-cell-derived NO is capable of degrading heparin and heparan sulphate via HNO2 rather than peroxynitrite. These observations may be relevant to various pathophysiological processes in which extracellular matrix is degraded, such as bone development, apoptosis, tissue damage from inflammatory responses and possible release of growth factors and cytokines.

Abstract 573: Endothelial α5 Integrins Regulate OxLDL-Induced Fibronectin Deposition, Proinflammatory Gene Expression, and Early Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Arif Yurdagul ◽  
Jonette Green ◽  
Wayne Orr
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Oxidized Ldl ◽  
Focal Adhesions ◽  
Published Data ◽  
Matrix Remodeling ◽  
Proinflammatory Gene ◽  
Fibronectin Deposition ◽  
Proinflammatory Gene Expression

Alterations in extracellular matrix quantity and composition contribute to atherosclerosis, with remodeling of the subendothelial basement membrane to a fibronectin-rich matrix preceding lesion development. Published data from our lab and others demonstrate that endothelial cell interactions with fibronectin prime inflammatory responses to a variety of atherogenic stimuli. However, the mechanisms regulating early atherogenic fibronectin accumulation remain unknown. Work from our group previously demonstrated that oxidized LDL (oxLDL) promotes endothelial proinflammatory gene expression by activating the integrin α5β1, a classic mediator of fibronectin fibrillogenesis. We now show that treating endothelial cells with oxLDL induces fibronectin deposition and inhibiting α5β1 (blocking antibodies, α5 knockout cells) completely inhibits oxLDL-induced fibronectin deposition. While endothelial fibronectin expression remains unchanged, oxLDL robustly stimulates the deposition of endothelial cell-derived fibronectin associated with a significant reduction in intracellular fibronectin. Interestingly, loss of endothelial cell-derived fibronectin, but not plasma fibronectin, prevents integrin α5 localization to focal adhesions, reduces fibronectin fibril length, and inhibits oxLDL-induced VCAM-1 expression. In addition, inducible endothelial-specific deletion of α5 integrins significantly blunts atherosclerotic plaque formation in ApoE knockout mice, suggesting an important role for this integrin in early endothelial activation. Taken together, our data demonstrate that oxLDL stimulates α5 integrin-dependent subendothelial matrix remodeling and endothelial proinflammatory gene expression through the deposition of fibronectin.

scholarly journals TNF-α activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions

2006 ◽  
Vol 291 (5) ◽  
pp. H2116-H2125 ◽  
Author(s):  
Ronen Sumagin ◽  
Ingrid H. Sarelius
Keyword(s):  
Spatial Distribution ◽  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Leukocyte Rolling ◽  
Cremaster Muscle ◽  
Rolling Velocity ◽  
Tnf Α ◽  
Arteriolar Wall ◽  
Microvessel Wall

The observation that leukocyte-endothelial cell (EC) interactions are localized to specific regions on the microvessel wall suggests that adhesion molecule distribution is not uniform. We investigated ICAM-1 distribution and leukocyte-EC interactions in blood-perfused microvessels (<80 μm) in cremaster muscle of anesthetized mice, using intravital confocal microscopy and immunofluorescent labeling. Variability of ICAM-1 expression directly determines leukocyte adhesion distribution within the venular microcirculation and contributes to leukocyte rolling in arterioles during inflammation. The number of rolling interactions increased with ICAM-1 intensity ( r2 = 0.69, P < 0.05), and rolling velocity was lower in regions of higher ICAM-1 intensity. In controls, venular ICAM-1 expression was approximately twofold higher than in arterioles. After TNF-α treatment, ICAM-1 expression was significantly increased, 2.8 ± 0.2-fold in arterioles and 1.7 ± 0.2-fold in venules ( P < 0.05). ICAM-1 expression on activated arteriolar ECs only reached the level of control venular ICAM-1. Arteriolar but not venular ECs underwent redistribution of ICAM-1 among cells; some cells increased and some decreased ICAM-1 expression, magnifying the variability of ICAM-1. TNF-α treatment increased the length of bright fluorescent regions per unit vessel length (42%, control; 70%, TNF-α) along the arteriolar wall, whereas no significant change was observed in venules (60%, control; 63%, TNF-α). The spatial distribution and expression levels of adhesion molecules in the microcirculation determine the timing and placement of leukocyte interactions and hence significantly impact the inflammatory response. That arteriolar ECs respond to TNF-α by upregulation of ICAM-1, although in a different way compared with venules, suggests an explicit role for arterioles in inflammatory responses.

scholarly journals Ufm1 inhibits LPS-induced endothelial cell inflammatory responses through the NF-κB signaling pathway

2017 ◽  
Vol 39 (5) ◽  
pp. 1119-1126 ◽  
Author(s):  
Yuan-Yuan Li ◽  
Guang-Ya Zhang ◽  
Jiang-Ping He ◽  
Dan-Dan Zhang ◽  
Xiang-Xin Kong ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Signaling Pathway ◽  
Inflammatory Responses

Receptors to interleukin-6 and adhesion molecules on circulating monocyte subsets in acute myocardial infarction

2013 ◽  
Vol 110 (08) ◽  
pp. 340-348 ◽  
Author(s):  
Benjami Wrigley ◽  
Silvia Montoro-Garcia ◽  
Eduard Shantsila ◽  
Luke Tapp ◽  
Gregory Lip
Keyword(s):  
Myocardial Infarction ◽  
Adhesion Molecule ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Stable Coronary Artery Disease ◽  
Annexin V ◽  
Receptor Expression ◽  
Tissue Type ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Subsets

SummaryThe role of individual monocyte subsets in inflammation and recovery post-myocardial infarction (MI) is insufficiently understood. It was the objective of this study to evaluate the dynamics of monocyte expression of receptors to vascular cell adhesion molecule (VCAM-1r), intercellular adhesion molecule (ICAM-1r), and interleukin-6 (IL-6r) following MI and their relation to inflammatory cytokines, fibrinolytic factors and annexin V-binding microparticles. Expression of VCAM-1r, ICAM-1r, IL-6r on CD14++CD16–(Mon1), CD14++CD16+(Mon2), CD14+CD16++(Mon3) monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (STEMI, n=50), non-STEMI (n=48) and stable coronary artery disease (n=40). In STEMI, parameters were measured on days 1, 3, 7, 30. On admission with STEMI, VCAM-1r expression was reduced on Mon1 (p=0.007), Mon2 (p=0.036), Mon3 (p=0.005), whilst in NSTEMI there was significant up-regulation of expression by Mon2 (p=0.024) and Mon3 (p=0.049). VCAM-1r on Mon1 correlated positively with plasma IL-1β levels (p=0.001). IL-6r was reduced on Mon2 in acute STEMI, with upregulation of the receptor on Mon1 and Mon2 during follow-up. IL-6r density correlated negatively with plasma levels of tissue-type plasminogen activator (p=0.0005 for Mon1, p=0.001 for Mon2 and Mon3), and positively with annexin V-binding microparticles (p=0.03 for Mon1, p=0.005 for Mon2 and p=0.005 for Mon3). There was no change in monocyte ICAM-1r expression. In conclusion, expression of IL-6r and VCAM-1r is reduced on circulating monocyte subsets involved in inflammatory responses in STEMI. This may represent a regulatory feed-back mechanism aiming to re-balance the marked inflammation which is typically present following acute MI or selective homing of monocytes with high receptor expression to damaged myocardium.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.

QS157. Mechanisms Other Than Acute Hyperglycemia Mediate Endothelial Cell Activation in Systemic Inflammatory Responses

2008 ◽  
Vol 144 (2) ◽  
pp. 329-330
Author(s):  
Peter B. Brant-Zawadzki ◽  
Andrew S. Weyrich ◽  
Guy A. Zimmerman ◽  
Larry W. Kraiss
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Endothelial Cell Activation ◽  
Acute Hyperglycemia
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