Resveratrol Suppresses Tumor Necrosis Factor-α-Induced Fractalkine Expression in Endothelial Cells

Moon, Sang Ok; Kim, Won; Sung, Mi Jeong; Lee, Sik; Kang, Kyung Pyo; Kim, Duk Hoon; Lee, Sang Yong; So, Jun No; Park, Sung Kwang

doi:10.1124/mol.106.022392

Cited by 57 publications

(50 citation statements)

References 42 publications

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“…It is also associated with the induction of an antitumor Th 1 response (21,32). Inflammation has been reported to induce NF-κB-dependent CX 3 CL1 upregulation in different tissues, through TNF-α, LPS or advanced glycation endproducts (30,33,34). This findings suggests that CX 3 CL1 plays an important role in inflammation; it also has a function under physiological conditions, however.…”

Section: Discussioncontrasting

confidence: 45%

“…CX 3 CL1 is upregulated under a variety of pathological conditions, such as vascular injury and tissue damage (30). It is responsible for the recruitment of natural killer cells to the brain during experimental autoimmune encephalitis (31), involved in asthma-associated mast cell chemotaxis (19), and chemotaxis of leukocytes in experimental autoimmune myositis (18).…”

Section: Discussionmentioning

confidence: 99%

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Fractalkine-Induced MFG-E8 Leads to Enhanced Apoptotic Cell Clearance by Macrophages

Miksa

Amin

et al. 2007

Mol Med

103

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Clearance of apoptotic cells is crucial to maintain cellular function under normal and pathological conditions. We have recently shown that administration of immature dendritic cell-derived exosomes to septic animals promotes phagocytosis of apoptotic cells and improves survival by providing milk fat globule epidermal growth factor-factor VIII (MFG-E8). MFG-E8 acts as an opsonin for apoptotic cells to be engulfed by phagocytosis. In the present study we investigated whether the CX 3 C-chemokine fractalkine (CX 3 CL1) promotes apoptotic cell clearance through the induction of MFG-E8 in peritoneal macrophages. Cultured rat peritoneal macrophages (pMφ) and RAW264.7 macrophages were stimulated with LPS and CX 3 CL1. MFG-E8 expression was assessed by Western blot, cytokine secretion was assessed by ELISA, and phagocytosis of apoptotic thymocytes was determined by microscopy. For in vivo studies, cecal ligation and puncture (CLP) was used to induce sepsis in rats and mice. LPS significantly decreased MFG-E8 levels and phagocytosis of apoptotic cells, whereas CX 3 CL1 induced MFG-E8 expression in both nonstimulated and LPS-stimulated pMφ, without affecting TNF-α and IL-6 release. Anti-MFG-E8 blocking antibodies completely abrogated the prophagocytic effect of CX 3 CL1. Twenty hours after the induction of sepsis in rats via CLP, plasma CX 3 CL1 levels as well as MFG-E8 production in peritoneal macrophages decreased by 21% and 56%, respectively. Administration of CX 3 CL1 on the other hand induced MFG-E8 and prevented tissue injury. We conclude that CX 3 CL1 induces MFG-E8 in vitro and in vivo and enhances clearance of apoptotic cells in an MFG-E8-dependent manner. These findings suggest a possible novel treatment for patients in sepsis.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Fractalkine-Induced MFG-E8 Leads to Enhanced Apoptotic Cell Clearance by Macrophages

Miksa

Amin

et al. 2007

Mol Med

103

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“…During endotoxemia, the vascular endothelial cells are affected by the inflammatory cytokines that induce the expression of cell adhesion molecules, such as ICAM-1, VCAM-1, and fractalkine (9,16). Following the expression of cell adhesion molecules, inflammatory cells, such as neutrophil and polymorphonuclear cells migrate into the tissue and are activated at the site of inflammation (18).…”

Section: Discussionmentioning

confidence: 99%

“…NF-κB activates and coordinates the inflammatory cascade in endotoxemia (9). To examine whether JAK3 is involved in this TNF-α-induced NF-κB activation, we assessed the TNF-α-induced NF-κB p65 phosphorylation by western blotting.…”

Section: Janex-1 Inhibits Tnf-α-induced Nf-κb Activation Inmentioning

confidence: 99%

“…Among these signaling pathways, the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway participates in the signaling of many cytokines and is involved in stress-responsive gene expression, immune response, myocardial ischemic preconditioning and the remodeling of post-myocardial infarction (5)(6)(7)(8). In response to proinflammatory stimuli in endotoxemia, the nuclear factor-κB (NF-κB) signaling pathway is activated and coordinates the inflammatory cascade (9). Interactions between NF-κB and STAT3 may play an important role in inflammation-mediated tumor progression and may control the production of proinflammatory cytokines and chemokines in immune cells (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice

Lee

Kim

et al. 2012

Int J Mol Med

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Abstract. Vascular endothelial cells play an important role in leukocyte trafficking during the inflammatory process. Proinflammatory cytokines activate the expression of cell adhesion molecules in endothelial cells. Janus kinase (JAK) and signal transducer and activator of transcription (STAT) are important intracellular cytokine signaling molecules that are involved in immune responses. The purpose of this study was to investigate the effect of JAK3 inhibition on the expression of tumor necrosis factor (TNF)-α-induced cell adhesion molecules in vascular endothelial cells and to evaluate the therapeutic potential of JAK3 for myocardial vascular permeability in endotoxemic mice. A JAK3 inhibitor, JANEX-1, decreased the TNF-α-induced expression of intercellular adhesion molecule (ICAM)-1, VCAM (vascular cell adhesion molecule)-1 and fractalkine in human umbilical vein endothelial cells (HUVECs). The downregulation of the expression of these cell adhesion molecules by JANEX-1 was mediated via suppression of STAT3 phosphorylation and nuclear factor-κB (NF-κB) activation. In endotoxemic mice, pretreatment with JANEX-1 prevented not only an increase in the cardiac ICAM-1 expression by LPS in the arteriolar and capillary endothelial cells, but also myocardial vascular leakage. These results suggest that inhibition of the JAK/STAT pathway by JANEX-1 ameliorates the expression of TNF-α-induced cell adhesion molecules in HUVECs and improves myocardial vascular permeability. IntroductionSepsis is a systemic inflammatory response to severe infection and is characterized by multi-organ dysfunction and hemodynamic compromise (1). A pathophysiological feature of sepsis is the production of proinflammatory mediators, such as cellular adhesion molecules, cytokines, and chemokines by vascular endothelial and inflammatory cells (2). Among these cells, the vascular endothelial cells play important roles both in forming a structural barrier between circulating blood and the underlying tissue and in generating vasoactive mediators, such as nitric oxide, prostacyclin, endothelin, and platelet-activating factor in response to physiological or pathological conditions (3). Infiltration of leukocytes from the circulatory system to the inflammatory site requires the expression of adhesion molecules and multiple signaling cascades in endothelial cells (3,4). Therefore, therapeutic strategies focused on the regulation of the interaction between circulating leukocytes and endothelial cells might be a plausible approach to treat sepsis-induced organ dysfunction.The first step in the initiation of inflammatory cascades is the binding of a cytokine to its corresponding receptor, leading to a change in gene expression. Among these signaling pathways, the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway participates in the signaling of many cytokines and is involved in stress-responsive gene expression, immune response, myocardial ischemic preconditioning and the remodeling of post-myocardial infarction (5-8). ...

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Resveratrol: Biochemistry and Functions

Das

Vasanthi

Das

2009

Plant Phenolics and Human Health

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Resveratrol Suppresses Tumor Necrosis Factor-α-Induced Fractalkine Expression in Endothelial Cells

Cited by 57 publications

References 42 publications

Fractalkine-Induced MFG-E8 Leads to Enhanced Apoptotic Cell Clearance by Macrophages

Fractalkine-Induced MFG-E8 Leads to Enhanced Apoptotic Cell Clearance by Macrophages

Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice

Resveratrol: Biochemistry and Functions

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