Relative contribution of the TNF-α receptors to murine intimal hyperplasia

2003 ◽  
Vol 284 (5) ◽  
pp. R1213-R1218 ◽  
Author(s):  
Michael A. Zimmerman ◽  
Leonid L. Reznikov ◽  
Amy C. Sorensen ◽  
Craig H. Selzman
Keyword(s):  
Vascular Injury ◽  
Intimal Hyperplasia ◽  
Nuclear Factor Κb ◽  
Arterial Injury ◽  
Receptor Subtype ◽  
Nuclear Factor ◽  
Relative Contribution ◽  
Tnf Α ◽  
Factor Α ◽  
Carotid Arterial

Tumor necrosis factor-α (TNF-α) is an important mediator in the inflammatory response to vascular injury. The present study sought to determine the relative contribution of each TNF-α receptor subtype (p55 and p75) to intimal hyperplasia (IH) and characterize the mechanisms of transcriptional regulation after vascular injury. A murine model of wire carotid arterial injury was employed to induce IH in wild-type (WT), p55-deficient (p55−/−), and p75-deficient (p75−/−) mice. Compared with injured WT and p75−/− animals, p55−/− mice demonstrated a twofold reduction in IH. Additionally, p55−/− mice demonstrated a decrease in expression of nuclear factor-κB mRNA and protein. These observations suggest an important role for the p55 receptor in IH after mechanical endoluminal injury. Suppression of the transcriptional activator nuclear factor-κB may provide a mechanism by which p55-mediated IH is attenuated.

N-acetylcysteine inhibited nuclear factor-κB expression and the intimal hyperplasia in rat carotid arterial injury

2001 ◽  
Vol 23 (7) ◽  
pp. 731-738 ◽  
Author(s):  
Kentaro Hayashi ◽  
Hideaki Takahata ◽  
Naoki Kitagawa ◽  
Gaspar Kitange ◽  
Makio Kaminogo ◽  
...  
Keyword(s):  
Intimal Hyperplasia ◽  
Nuclear Factor Κb ◽  
Arterial Injury ◽  
Nuclear Factor ◽  
Carotid Arterial

A direct requirement of nuclear factor-κB for suppression of apoptosis in ventricular myocytes

2000 ◽  
Vol 279 (3) ◽  
pp. H939-H945 ◽  
Author(s):  
Shareef Mustapha ◽  
Alla Kirshner ◽  
Danielle De Moissac ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Vital Staining ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cytoplasmic Factor ◽  
Tnf Α ◽  
Factor Α

Nuclear factor-κB (NF-κB) is a ubiquitously expressed cellular factor regulated by the cytoplasmic factor inhibitor protein κBα (IκBα). Activation of NF-κB by cytokines, including tumor necrosis factor-α (TNF-α), requires the phosphorylation and degradation of IκBα. An anti-apoptotic role for NF-κB has recently been suggested. In the present study, we ascertained whether death-promoting signals and apoptosis mediated by TNF-α are suppressed by NF-κB in postnatal ventricular myocytes. Stimulation of myocytes with TNF-α resulted in a 12.1-fold increase ( P < 0.01) in NF-κB-dependent gene transcription and DNA binding compared with controls. This was accompanied by a corresponding increase in the NF-κB target protein A20 as determined by Western blot analysis. Vital staining revealed that TNF-α was not cytotoxic to myocytes and did not provoke apoptosis. Adenovirus-mediated delivery of a nonphosphorylatable form of IκBα to inactivate NF-κB prevented TNF-α-stimulated NF-κB-dependent gene transcription and nuclear NF-κB DNA binding. Importantly, myocytes stimulated with TNF-α and defective for NF-κB activation resulted in a 2.2-fold increase ( P < 0.001) in apoptosis. To our knowledge, the data provide the first indication that a functional NF-κB signaling pathway is crucial for suppressing death-promoting signals mediated by TNF-α in ventricular myocytes.

Activated Protein C Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production by Inhibiting Activation of both Nuclear Factor-κB and Activator Protein-1 in Human Monocytes

2002 ◽  
Vol 88 (08) ◽  
pp. 267-273 ◽  
Author(s):  
Mehtap Yuksel ◽  
Mitsuhiro Uchiba ◽  
Seikoh Horiuchi ◽  
Hiroaki Okabe ◽  
Kenji Okajima
Keyword(s):  
Protein C ◽  
Tumor Necrosis ◽  
Activated Protein C ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Tnf Α ◽  
Target Sites ◽  
Factor Α ◽  
Necrosis Factor

SummaryActivated protein C (APC), an important natural anticoagulant, inhibits tumor necrosis factor-α (TNF-α) production and attenuates various deleterious events induced by lipopolysaccharide (LPS), contributing thereby to a significant reduction of mortality in patients with severe sepsis. In this study, we investigated the mechanism(s) by which APC inhibits TNF-α production by LPS-stimulated human monocytes in vitro. Although APC inhibited LPS-induced TNF-α production in a concentration-dependent fashion, diisopropyl fluorophosphate-treated APC, an active-site-blocked APC, had no effect. APC inhibited both the binding of nuclear factor-κB (NF-κB) to target sites and the degradation of IκBα. APC also inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. These observations strongly suggest that APC inhibited LPS-induced TNF-α production by inhibiting the activation of both NF-κB and AP-1 and that the inhibitory activity of APC might depend on its serine protease activity. These results would at least partly explain the mechanism(s) by which APC reduces the tissue injury seen in animal models of sepsis and in patients with sepsis.

Thyrotropin modifies activation of nuclear factor κB by tumour necrosis factor α in rat thyroid cell line

2001 ◽  
Vol 354 (3) ◽  
pp. 573-579 ◽  
Author(s):  
Toyone KIKUMORI ◽  
Fukushi KAMBE ◽  
Takashi NAGAYA ◽  
Hiroomi FUNAHASHI ◽  
Hisao SEO
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Nuclear Factor Κb ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Rat Thyroid ◽  
Factor Α ◽  
Necrosis Factor

We have recently demonstrated that nuclear factor κB (NF-κB) mediates the tumour necrosis factor α (TNF-α)-dependent expression of the gene encoding interleukin 6 (IL-6) in rat thyroid FRTL-5 cells cultured in the presence of thyrotropin (TSH). In the present study we investigated how TSH is involved in the activation of NF-κB by TNF-α in the cells. Electrophoretic mobility-shift assay revealed that, in the absence of TSH, TNF-α activated a single protein–DNA complex containing the p50 subunit but not other NF-κB subunits such as p65. In contrast, two distinct protein–DNA complexes were activated in the presence of TSH: the faster-migrating complex contained only p50 subunit; the slower-migrating complex consisted of p65–p50heterodimer. This TSH effect was mimicked by forskolin and thyroid-stimulating antibodies obtained from patients with Graves's disease, suggesting that an increase in intracellular cAMP is responsible for the induction of different NF-κBs by TNF-α. A transient transfection study with a luciferase reporter gene driven by multimerized NF-κB sites demonstrated that TNF-α increased the luciferase activities only in the presence of TSH, and that this increase was inhibited by the co-transfection of mutant p65, which prevented the function of wild-type p65 in a dominant-negative manner. Accordingly, TNF-α activated the expression of the IL-6 gene in the presence of TSH but not in its absence. Although the expression of the p105 gene, another known target for NF-κB, was increased by TNF-α in the absence of TSH, the presence of TSH further increased the mRNA level. Taken together, these observations indicate that the presence of TSH is crucial for the NF-κB-mediated actions of TNF-α on thyroid follicular cells.

Monoammonium glycyrrhizate suppresses tumor necrosis factor-α induced chemokine production in HMEC-1 cells, possibly by blocking the translocation of nuclear factor-κB into the nucleus

2014 ◽  
Vol 92 (10) ◽  
pp. 859-865 ◽  
Author(s):  
Na Cao ◽  
Tao Chen ◽  
Zai-pei Guo ◽  
Sha Qin ◽  
Meng-meng Li
Keyword(s):  
Tumor Necrosis ◽  
Skin Diseases ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Inflammatory Skin Diseases ◽  
Chemokine Production ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Monoammonim glycyrrhizate (MAG) derived from licorice has been shown to have anti-inflammatory properties. Chemokines are vital inflammatory mediators that are involved with endothelial damage from leukocyte infiltrates in various inflammatory skin diseases. In this study, we investigated the anti-inflammatory effects and mechanisms of MAG on tumor necrosis factor-α (TNF-α) induced chemokine production in a human dermal microvascular endothelial cell line (HMEC-1). HMEC-1 cells were treated with TNF-α, with or without MAG. The results showed that MAG suppressed TNF-α-induced chemokine (including CXCL8, CX3CL1, and CXCL16) mRNA expression in HMEC-1 cells, in a dose-dependent manner, and reduced the secretion of these chemokines in culture supernatant. Moreover, endothelial activation in the presence of MAG blocked the chemotactic activities of TNF-α-stimulated HMEC-1 cell supernatant on the migration of primary neutrophils and primary monocytes. In addition, Western blot and immunofluorescence data revealed that MAG inhibited nuclear translocation of nuclear factor-κB p65 (NF-κB p65). It is the first report to demonstrate that MAG suppresses TNF-α-induced chemokine production in HMEC-1 cells, and that the mechanism may be inhibiting the translocation of NF-κB p65 into the nucleus to prevent the starting of inflammatory signaling pathway. Our results revealed that MAG is a potential anti-inflammatory agent capable of improving inflammatory skin diseases.

I. TNF-induced liver injury

1998 ◽  
Vol 275 (3) ◽  
pp. G387-G392 ◽  
Author(s):  
Cynthia A. Bradham ◽  
Jörg Plümpe ◽  
Michael P. Manns ◽  
David A. Brenner ◽  
Christian Trautwein
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Κb ◽  
Hepatocyte Proliferation ◽  
Nuclear Factor ◽  
Normal Hepatocyte ◽  
Tnf Α ◽  
Factor Α ◽  
Transcription Factor Nuclear Factor ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α) functions as a two-edged sword in the liver. TNF-α is required for normal hepatocyte proliferation during liver regeneration. It functions both as a comitogen and to induce the transcription factor nuclear factor-κB, which has antiapoptotic effects. On the other hand, TNF-α is the mediator of hepatotoxicity in many animal models, including those involving the toxins concanavalin A and lipopolysaccharide. TNF-α has also been implicated as an important pathogenic mediator in patients with alcoholic liver disease and viral hepatitis.

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