scholarly journals Isolation and Characterization of the Fungal Metabolite 3-O-Methylviridicatin as an Inhibitor of Tumour Necrosis Factor α-Induced Human Immunodeficiency Virus Replication

1998 ◽  
Vol 9 (2) ◽  
pp. 149-155 ◽  
Author(s):  
A Heguy ◽  
P Cai ◽  
P Meyn ◽  
D Houck ◽  
S Russo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Line ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Luciferase Reporter ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Α ◽  
Necrosis Factor

The cytokine tumour necrosis factor α (TNF-α) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-α-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-α induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR–luciferase reporter plasmid and a stable line was isolated in which TNF-α increased luciferase production by two- to threefold. This cell line was used to screen approximately 15 000 fungal extracts. An inhibitory activity specific for TNF-α-induced HIV LTR transcription was observed in culture OS-F67406. The active component was isolated and identified as a known metabolite, 3-O-methylviridicatin, by NMR and mass spectrometry. No biological activity has been associated with this compound previously. This compound blocks TNF-α activation of the HIV LTR in the HeLa-based system, with an IC50 of 5 μM, and inhibited virus production in the OM-10.1 cell line, a model of chronic infection responsive to induction by TNF-α, with an IC50 of 2.5 μM.

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.

Differential effect of selective block of α2-adrenoreceptors on plasma levels of tumour necrosis factor-α, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice

1995 ◽  
Vol 144 (3) ◽  
pp. 457-462 ◽  
Author(s):  
G Haskó ◽  
I J Elenkov ◽  
V Kvetan ◽  
E S Vizi
Keyword(s):  
Tumour Necrosis Factor ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Tumour Necrosis ◽  
Endotoxin Shock ◽  
Bacterial Lipopolysaccharide ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract The effect of selective block of α2-adrenoreceptors on plasma levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. It was found that the LPS-induced TNF-α response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective α2-adrenoreceptor antagonist (the α2/α1 ratio is >2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of α2-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of α2-adrenoreceptor blockade on TNF-α plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of β-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-α is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of α2-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock. Journal of Endocrinology (1995) 144, 457–462

scholarly journals Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages

2016 ◽  
Vol 36 (1) ◽  
Author(s):  
Abbas Jawad Al-Shabany ◽  
Alan John Moody ◽  
Andrew David Foey ◽  
Richard Andrew Billington
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Cytokine ◽  
Bacterial Lipopolysaccharide ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Inflammatory Macrophages ◽  
Inflammatory Macrophage ◽  
Necrosis Factor

Bacterial lipopolysaccharide induces changes in intracellular NAD+ levels in a pro-inflammatory, but not an anti-inflammatory, macrophage model that are correlated with the release of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α).

scholarly journals JFC1 is transcriptionally activated by nuclear factor-κB and up-regulated by tumour necrosis factor α in prostate carcinoma cells

2002 ◽  
Vol 367 (3) ◽  
pp. 791-799 ◽  
Author(s):  
Sergio D. CATZ ◽  
Bernard M. BABIOR ◽  
Jennifer L. JOHNSON
Keyword(s):  
Tumour Necrosis Factor ◽  
Cell Lines ◽  
Prostate Carcinoma ◽  
Tumour Necrosis ◽  
Nuclear Factor Κb ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

The human promoter region of JFC1, a phosphatidylinositol 3,4,5-trisphosphate binding ATPase, was isolated by amplification of a 549bp region upstream of the jfc1 gene by the use of a double-PCR system. By primer extension analysis we mapped the transcription initiation site at nucleotide −321 relative to the translation start site. Putative regulatory elements were identified in the jfc1 TATA-less promoter, including three consensus sites for nuclear factor-κB (NF-κB). We analysed the three putative NF-κB binding sites by gel retardation and supershift assays. Each of the putative NF-κB sites interacted specifically with recombinant NF-κB p50, and the complexes co-migrated with those formed by the NF-κB consensus sequence and p50. An antibody to p50 generated a supershifted complex for these NF-κB sites. These sites formed specific complexes with nuclear proteins from tumour necrosis factor α (TNFα)-treated WEHI 231 cells, which were supershifted with antibodies against p50 and p65. The jfc1 promoter was transcriptionally active in various cell lines, as determined by luciferase reporter assays following transfection with a jfc1 promoter luciferase vector. Co-transfection with NF-κB expression vectors or stimulation with TNFα resulted in significant transactivation of the jfc1 promoter construct, although transactivation of a mutated jfc1 promoter was negligible. The expression of a dominant negative IκB (inhibitor κB) decreased basal jfc1 promoter activity. The cell lines PC-3, LNCaP and DU-145, but not Epstein—Barr virus-transformed lymphocytes, showed a dramatic increase in the expression of JFC1 after treatment with TNFα, suggesting that transcriptional activation of JFC1 by the TNFα/NF-κB pathway is significant in prostate carcinoma cell lines.

scholarly journals The Influence of Interleukin (IL)-1β and IL-6 and Tumour Necrosis Factor-α on Prostaglandin Secretion from Porcine Myometrium during the First Third of Pregnancy

2010 ◽  
Vol 79 (4) ◽  
pp. 559-569 ◽  
Author(s):  
Barbara Jana ◽  
Marlena Koszykowska ◽  
Aneta Andronowska
Keyword(s):  
Protein Expression ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Uterine Contraction ◽  
Tumour Necrosis Factor Α ◽  
Cytokine Network ◽  
Tnf Α ◽  
Cox 2 ◽  
Factor Α ◽  
Necrosis Factor

The present study was undertaken to determine the effect of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) on prostaglandin (PG)F2α and PGE2 secretion as well as cyclooxygenase-2 (COX-2) protein expression in myometrium collected on days 25, 30 and 40 of pregnancy in pigs. Myometrial slices were incubated for 16 h with IL-1β, IL-6 and TNF-α (1 or 10 ng/ml of medium) or two combinations of the three cytokines (1 or 10 ng/ml of each cytokine per combination). We demonstrated the stimulatory effect of IL-1β and IL-6 on PGF2α and PGE2 secretion from myometrium collected on all examined days of pregnancy, excepting of influence of IL-6 on release of PGF2α by tissue from day 30. In turn, TNF-α was able to stimulate only PGE2 secretion by myometrium of 40-day-pregnant gilts. The three cytokines applied in combination augmented release of PGE2 from myometrium collected on days 30 and 40 of pregnancy. Stimulation of PGE2 secretion by cytokines used individually was more frequent than that of PGF2α. Moreover, an enhancement in PGF2α and/or PGE2 release was accompanied by an increase of COX-2 protein expression. Our study shows the ability of cytokines to stimulate PGF2α and PGE2 release by porcine myometrium from the first third of pregnancy. Obtained data suggest that locally PGs produced in myometrium influencing the uterine contraction activity may be important for the maintenance of myometrial quiescence during pregnancy and confirm also that the complex cytokine network is an important regulatory mechanism of PGs production during pregnancy.

Levels of Serum Interleukin (IL)-6, IL-1β, Tumour Necrosis Factor-α and Leptin and Their Correlation in Depression

2007 ◽  
Vol 41 (3) ◽  
pp. 266-273 ◽  
Author(s):  
Kun Yang ◽  
Guangrong Xie ◽  
Zhongxing Zhang ◽  
Changhong Wang ◽  
Wenbo Li ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Serum Levels ◽  
Tumour Necrosis Factor Α ◽  
Depressed Patients ◽  
Tnf Α ◽  
Male Patients ◽  
Factor Α ◽  
Normal Controls ◽  
Necrosis Factor

Objective: To investigate the relationship between leptin and cytokines in depressed patients. Methods: Thirty-three unmedicated patients (24 female, nine male) with depressive disorder and 23 healthy controls (16 female, seven male) were assessed for serum levels of interleukin (IL)-6, IL-1β, tumour necrosis factor-α (TNF-α) and leptin. Results: Levels of IL-6 and TNF-α in depressed patients were higher than in normal controls. There were significantly lower leptin levels in depressed patients than in normal controls. There were also significant differences in the leptin levels, being higher in female than in male patients, and in female than in male controls. Conclusions: IL-6 and TNF-α cytokines and leptin are important in the psychoimmunology of depressed patients. There were gender differences in leptin levels in depression.

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