High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

1995 ◽  
Vol 63 (2) ◽  
pp. 591-595 ◽  
Author(s):  
M T Rivera ◽  
S Marques de Araujo ◽  
R Lucas ◽  
J Deman ◽  
C Truyens ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Pregnant Mice ◽  
Factor Alpha ◽  
Alpha Gene ◽  
Necrosis Factor

scholarly journals 2-Aminopurine selectively inhibits splicing of tumor necrosis factor alpha mRNA.

1996 ◽  
Vol 16 (6) ◽  
pp. 2814-2822 ◽  
Author(s):  
N Jarrous ◽  
F Osman ◽  
R Kaempfer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Translation Initiation Factor ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Rnase Protection ◽  
Factor Alpha ◽  
Alpha Gene ◽  
Necrosis Factor

2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid cells. 2-AP does not inhibit transcription of the human TNF-alpha gene, nor does it affect mRNA stability. Instead, the flow of short-lived precursor transcripts into mature TNF-alpha mRNA is blocked. When 2-AP is present during induction, unspliced TNF-alpha precursor transcripts accumulate at the expense of mRNA. Using RNase protection analysis with genomic probes for different exon-intron junctions, we show that 2-AP blocks splicing of TNF-alpha mRNA. Neither the TNF-beta nor the interleukin-1 beta gene shows such regulation. 2-AP also inhibits splicing of precursor RNA transcribed from an exogenous human TNF-alpha gene. Sequences within this gene thus confer sensitivity to 2-AP. Yet, control is not exerted at a specific splice site. Our results reveal the involvement of a 2-AP-sensitive component, expressed in functional form before induction, in the splicing of TNF-alpha mRNA.

scholarly journals Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease.

1992 ◽  
Vol 175 (2) ◽  
pp. 405-413 ◽  
Author(s):  
F P Nestel ◽  
K S Price ◽  
T A Seemayer ◽  
W S Lapp
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Acute Gvhd ◽  
Tnf Alpha ◽  
Triggered Release ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Factor Alpha ◽  
Necrosis Factor

In this report we have investigated macrophage (M phi) activity and tumor necrosis factor alpha (TNF-alpha) production during graft-vs.-host disease (GVHD). TNF-alpha production by M phi requires two signals: priming of M phi by interferon followed by triggering of TNF-alpha production and release by lipopolysaccharide (LPS). The state of M phi activation was examined in nonirradiated B6AF1 recipient mice injected with either 60 x 10(6) (acute GVHD) or 30 x 10(6) (nonlethal GVHD) parental B6 lymphoid cells. During the early phase of acute GVHD, administration of normally sublethal amounts of LPS-triggered release of significant amounts of TNF-alpha into the serum resulting in death of the animals within 36 h. Normal animals treated with the same dose of LPS neither died nor produced detectable amounts of serum TNF-alpha. In vitro studies demonstrated that M phi were primed during GVHD. The level of M phi priming was greater during acute GVHD than nonlethal GVHD since 100-fold less LPS was required to trigger killing of a TNF-alpha-sensitive cell line by M phi from acute GVHD animals. The amount of TNF-alpha released into the serum after LPS injection increased during the course of the GVHD and was significantly greater in acute GVH-reactive mice. Endogenous LPS was detected in the serum of acute GVH-reactive animals coincident with the onset of mortality. The data provide evidence that during GVHD M phi are primed as a result of the allogeneic reaction and that endogenous LPS therefore triggers M phi production of TNF-alpha resulting in the symptoms characteristic of acute GVHD.

scholarly journals Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis.

1994 ◽  
Vol 179 (3) ◽  
pp. 841-848 ◽  
Author(s):  
R González-Amaro ◽  
C García-Monzón ◽  
L García-Buey ◽  
R Moreno-Otero ◽  
J L Alonso ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Kupffer Cells ◽  
Human Liver ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine that has an important role in the pathogenesis of inflammation, cachexia, and septic shock. Although TNF-alpha is mainly produced by macrophages, there is evidence regarding TNF-alpha production by cells that are not derived from bone marrow. TNF-alpha production by normal and inflamed human liver was assessed at both mRNA and protein levels. Using a wide panel of novel anti-TNF-alpha monoclonal antibodies and a specific polyclonal antiserum, TNF-alpha immunoreactivity was found in hepatocytes from patients chronically infected with either hepatitis B virus (HBV) or hepatitis C virus. Minimal TNF-alpha immunoreactivity was detected in the mononuclear cell infiltrate and Kupffer cells. In situ hybridization experiments using a TNF-alpha RNA probe showed a significant expression of TNF-alpha mRNA in hepatocytes, Kupffer cells, and some infiltrating mononuclear cells. By contrast, TNF-alpha was detected at low levels in liver biopsies from normal individuals or patients with alcoholic liver disease and low expression of TNF-alpha mRNA was observed in these specimens. Transfection of HepG2 hepatoblastoma cells with either HBV genome or HBV X gene resulted in induction of TNF-alpha expression. Our results demonstrate that viral infection induces, both in vivo and in vitro, TNF-alpha production in hepatocytes, and indicate that the HBV X protein may regulate the expression of this cytokine. These findings suggest that TNF-alpha may have an important role in human liver diseases induced by viruses.

scholarly journals Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation.

1993 ◽  
Vol 177 (6) ◽  
pp. 1675-1680 ◽  
Author(s):  
A L Moreira ◽  
E P Sampaio ◽  
A Zmuidzinas ◽  
P Frindt ◽  
K A Smith ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Synergistic Effects ◽  
Selective Inhibition ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Factor Alpha ◽  
Necrosis Factor

We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production and found that the drug enhances the degradation of TNF-alpha mRNA. Thus, the half-life of the molecule was reduced from approximately 30 to approximately 17 min in the presence of 50 micrograms/ml of thalidomide. Inhibition of TNF-alpha production was selective, as other LPS-induced monocyte cytokines were unaffected. Pentoxifylline and dexamethasone, two other inhibitors of TNF-alpha production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-alpha synthesis at distinct points of the cytokine biosynthetic pathway. These observations provide an explanation for the synergistic effects of these drugs. The selective inhibition of TNF-alpha production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-alpha-induced toxicities are observed and where immunity must remain intact.

scholarly journals Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp.

1996 ◽  
Vol 16 (2) ◽  
pp. 459-467 ◽  
Author(s):  
E Y Tsai ◽  
J Jain ◽  
P A Pesavento ◽  
A Rao ◽  
A E Goldfeld
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Gene Transcription ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Alpha Gene ◽  
Necrosis Factor

The human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest genes expressed upon the activation of a T or B cell through its antigen receptor. Previous experiments have demonstrated that in stimulated T cells, a TNF-alpha promoter element, kappa 3, which binds NFATp, is required for the cyclosporin A-sensitive transcriptional activation of the gene. Here, we demonstrate that a cyclic AMP response element (CRE), which lies immediately upstream of the kappa 3 site, is also required for induction of TNF-alpha gene transcription in T cells stimulated by calcium ionophore or T-cell receptor ligands. The CRE binds ATF-2 and Jun proteins in association with NFATp bound to kappa 3. These proteins bind noncooperatively in vitro; however, the transcriptional activity of the CRE/kappa 3 composite site is dramatically higher than the activity of the kappa 3 site alone, indicating that the two sites cooperate in vivo. This study is the first demonstration of a role for ATF-2 in TNF-alpha gene transcription and of a functional interaction between ATF-2/Jun and NFATp. This novel pairing of NFATp with ATF-2/Jun may account for the specific and immediate pattern of TNF-alpha gene transcription in stimulated T cells.

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