Effect of interleukin-1β and tumor necrosis factor-α  on gene expression in human endothelial cells

Zhao, Bin; Stavchansky, Salomon A; Bowden, Robert A.; Bowman, Phillip D.

doi:10.1152/ajpcell.00243.2002

Cited by 68 publications

(59 citation statements)

References 28 publications

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“…2,12,13 It is hardly surprising that blocking the action of endogenous IL-1b and TNFa release by cut explants of adipose tissue reduced the upregulation of MCP-1. These cytokines induce similar genes in human umbilical vein endothelial cells where Zhao et al 35 found that it was necessary to suppress both cytokines simultaneously in order to ameliorate the inflammatory response. Similarly, we found that inhibition of the up-regulation of MCP-1 in human visceral adipose tissue explants over 48 h was markedly reduced (À58%) in the presence of antagonists of both IL-1b and TNFa.…”

Section: Discussionmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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Section: Discussionmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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“…The overlap between the sets of genes activated in NIH3T3 cells by NO and by cytokines may reflect an important role for NO in the response of fibroblasts to cytokines in vivo during inflammation and tissue repair. It will be interesting to compare these results with the transcriptional profiles of cells exposed to individual cytokines (21)(22)(23)(24)(25) to estimate the relative contribution of NO in the action of these effectors.…”

Section: Effect Of Signaling Pathway Blockades On No-stimulated Gene mentioning

confidence: 99%

Nitric Oxide Activates Diverse Signaling Pathways to Regulate Gene Expression

Hemish

Nakaya

Mittal

et al. 2003

Journal of Biological Chemistry

133

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Nitric oxide signaling is crucial for effecting long lasting changes in cells, including gene expression, cell cycle arrest, apoptosis, and differentiation. We have determined the temporal order of gene activation induced by NO in mammalian cells and have examined the signaling pathways that mediate the action of NO. Using microarrays to study the kinetics of gene activation by NO, we have determined that NO induces three distinct waves of gene activity. The first wave is induced within 30 min of exposure to NO and represents the primary gene targets of NO. It is followed by subsequent waves of gene activity that may reflect further cascades of NO-induced gene expression. We verified our results using quantitative real time PCR and further validated our conclusions about the effects of NO by using cytokines to induce endogenous NO production. We next applied pharmacological and genetic approaches to determine the signaling pathways that are used by NO to regulate gene expression. We used inhibitors of particular signaling pathways, as well as cells from animals with a deleted p53 gene, to define groups of genes that require phosphatidylinositol 3-kinase, protein kinase C, NF-B, p53, or combinations thereof for activation by NO. Our results demonstrate that NO utilizes several independent signaling pathways to induce gene expression.Nitric oxide regulates a wide range of physiological responses (1). Most of the studies of NO action in animals have focused on its activity as an effector of rapid responses, such as regulation of blood pressure, smooth muscle contraction, and neurotransmission in the central and peripheral nervous systems. In these contexts, NO action is mediated by fast acting signaling cascades, which rapidly subside after the disappearance of the original stimulus (e.g. calcium influx).NO can also stimulate signaling pathways that elicit long lasting changes in the cell, and it can also reset genetic programs. This function of NO is manifested in its ability to regulate gene expression (2), to mediate immune response and inflammation (3), and to act as an antiproliferative factor to mediate tissue differentiation and organ development (4, 5). The molecular basis of these long lasting effects of NO is still unclear. To reveal the targets of NO in the cell, it will be important to understand the signaling pathways that are activated in response to NO.To investigate mechanisms underlying the long term action of NO, we used DNA microarrays to determine the temporal expression profiles of genes that respond to NO. We identified genes that are affected by NO and analyzed the temporal patterns of their expression to reveal cascades of NO-dependent gene regulation events. These results were verified by using quantitative real time PCR and validated by demonstrating that similar genes are activated in an NO-dependent manner in response to cytokines. We next used chemical inhibitors of specific signaling molecules and a mutant cell line to determine the signaling pathways that lead to the activation of spe...

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“…IL-1 and TNF-␣ are important mediators leading to increased expression of adhesion molecules E-selectin, VCAM-1, and ICAM-1 as well as expression of soluble proinflammatory cytokines, e.g., MCP-1, M-CSF, IL-6, and IL-8, by the endothelium (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The subsequent recruitment of leukocytes to inflamed tissue requires their tethering and rolling as well as rapid activation of integrin-dependent arrest on the target endothelium as a checkpoint for diapedesis to the extravascular tissue (17,18).…”

mentioning

confidence: 99%

Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness

Richter¹,

Bistrian

Escher³

et al. 2005

The Journal of Immunology

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Monocyte infiltration into inflammatory sites is generally preceded by neutrophils. We show here that neutrophils may support this process by activation of CCL15, a human chemokine circulating in blood plasma. Neutrophils were found to release CCL15 proteolytic activity in the course of hemofiltration of blood from renal insufficiency patients. Processing of CCL15 immunoreactivity (IR) in the pericellular space is suggested by a lack of proteolytic activity in blood and blood filtrate, but a shift of the retention time (tR) of CCL15-IR, detected by chromatographic separation of CCL15-IR in blood and hemofiltrate. CCL15 molecules with N-terminal deletions of 23 (Δ23) and 26 (Δ26) aa were identified as main proteolytic products in hemofiltrate. Neutrophil cathepsin G was identified as the principal protease to produce Δ23 and Δ26 CCL15. Also, elastase displays CCL15 proteolytic activity and produces a Δ21 isoform. Compared with full-length CCL15, Δ23 and Δ26 isoforms displayed a significantly increased potency to induce calcium fluxes and chemotactic activity on monocytes and to induce adhesiveness of mononuclear cells to fibronectin. Thus, our findings indicate that activation of monocytes by neutrophils is at least in part induced by quantum proteolytic processing of circulating or endothelium-bound CCL15 by neutrophil cathepsin G.

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Effect of interleukin-1β and tumor necrosis factor-α on gene expression in human endothelial cells

Abstract: . Effect of interleukin-1␤ and tumor necrosis factor-␣ on gene expression in human endothelial cells.

Cited by 68 publications

References 28 publications

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Nitric Oxide Activates Diverse Signaling Pathways to Regulate Gene Expression

Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness

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