scholarly journals Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis.

1995 ◽  
Vol 182 (5) ◽  
pp. 1259-1264 ◽  
Author(s):  
M Cabrera ◽  
M A Shaw ◽  
C Sharples ◽  
H Williams ◽  
M Castes ◽  
...  
Keyword(s):  
Relative Risk ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Leishmania Braziliensis ◽  
High Relative Risk ◽  
Heterozygous Condition ◽  
Mucocutaneous Leishmaniasis ◽  
Risk Of Disease ◽  
Necrosis Factor

Recent studies have shown that mucocutaneous leishmaniasis (MCL), a severe and debilitating form of American cutaneous leishmaniasis (ACL) caused by Leishmania braziliensis infection, is accompanied by high circulating levels of tumor necrosis factor (TNF)-alpha. Analysis of TNF polymorphisms in Venezuelan ACL patients and endemic unaffected controls demonstrates a high relative risk (RR) of 7.5 (P < 0.001) of MCL disease in homozygotes for allele 2 of a polymorphism in intron 2 of the TNF-beta gene, especially in females (RR = 9.5; P < 0.001) compared with males (RR = 4; P < 0.05). A significantly higher frequency (P < 0.05) of allele 2 at the -308-basepair TNF-alpha gene polymorphism was also observed in MCL patients (0.18) compared with endemic control subjects (0.069), again associated with a high relative risk of disease (RR = 3.5; P < 0.05) even in the heterozygous condition. Because both the TNF-alpha and TNF-beta polymorphisms have previously been linked with functional differences in TNF-alpha levels, these data suggest that susceptibility to the mucocutaneous form of disease may be directly associated with regulatory polymorphisms affecting TNF-alpha production.

scholarly journals Tumor necrosis factor (TNF)-induced protein phosphorylation in a human rhabdomyosarcoma cell line is mediated by 60-kD TNF receptors (TR60)

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2211-2220 ◽  
Author(s):  
A Mire-Sluis ◽  
A Meager
Keyword(s):  
Tumor Necrosis Factor ◽  
Protein Phosphorylation ◽  
Cell Line ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Tnf Receptors ◽  
Protein Kinase C Inhibitors ◽  
Rhabdomyosarcoma Cell Line ◽  
Rhabdomyosarcoma Cell ◽  
Necrosis Factor

Abstract In the present study, we used a cloned derivative, KYM-1D4, of the human rhabdomyosarcoma cell line, KYM-1, known to express high numbers of the two tumor necrosis factor (TNF) receptors, TR60 and TR80, and to be highly sensitive to TNF alpha-mediated cytotoxicity/antiproliferation, to investigate the role of TR60 and TR80 in protein phosphorylation. Using permeabilized KYM-1D4 cells, it was found that TNF alpha strongly induced phosphorylation of proteins of molecular weight 80, 65, 58, 42, and 30 kD. Addition of a monoclonal antibody (MoAb) against TR60 was shown to induce cytotoxicity/antiproliferation in KYM-1D4 cells and the same pattern of protein phosphorylation as TNF alpha, whereas addition of an MoAb against TR80 was both noncytotoxic and ineffective in inducing protein phosphorylation. In contrast, in a highly TNF alpha-resistant KYM-1- derived cell line, 37B8R, no protein phosphorylation was induced with either TNF alpha or the agonistic anti-TR60 MoAb. However, when 37B8R was allowed to revert to partial TNF sensitivity by culture in the absence of TNF alpha, the resultant cell line, 37B8S, was found to regain inducibility of protein phosphorylation by TNF alpha. These results indicate that expression of functional TR60 in KYM-1-related cell lines is principally involved in TNF-mediated cytotoxicity/antiproliferation and is necessary for the induction of protein phosphorylation. Nevertheless, the latter, although apparently strongly associated with cytotoxicity, was probably involved in protective mechanisms because protein kinase C inhibitors that inhibited TNF alpha and anti-TR60-induced phosphorylation increased the cytotoxic/antiproliferative response to these mediators.

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

ROLE OF INTER LEUKIN 10 AND TUMOR NECROSIS FACTOR-ΑLPHA IN PANCREATITIS

2021 ◽  
pp. 14-17
Author(s):  
Mukherjee.J. R ◽  
Mukherjee. B ◽  
Roy. S ◽  
Jana. D ◽  
Bandopadhyay. S ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
General Surgery ◽  
Tumor Necrosis ◽  
Cell Injury ◽  
Gall Stone ◽  
Tnf Alpha ◽  
Tnf Α ◽  
The Mean ◽  
Necrosis Factor

Background: Pancreatic acinar cell injury triggers the synthesis and release of pro-inammatory cytokines and chemokines. The involvement of several pro-inammatory and anti-inammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33 and tumor necrosis factor-α is involved in the pathogenesis of pancreatitis. Aim: This study aims to validate the role of activation of TNF-alpha and IL-10 as a biomaker marker in patients with Pancreatitis in Indian subcontinent.Material and methods: 50 Patients of Pancreatitis attending general surgery OPD and admitted to General Surgery department of SSKM Hospital, Kolkata, West Bengal, India were taken. Result: It was found that in alcoholic, the mean TNF - α (mean±s.d.) of the patients was 19.4027 ± 8.3275 pg/ml. In ascites, the mean TNF - α (mean±s.d.) of the patients was 19.9767 ± 2804 pg/ml. In chronic, the mean TNF - α (mean±s.d.) of the patients was 18.8533 ± 8.4674 pg/ml. In gall stone, the mean TNF - α (mean±s.d.) of the patients was 16.3421 ± 9.9499 pg/ml. In osteoarthritis, the mean TNF - α (mean±s.d.) of the patients was 12.4750 ± 8.3085 pg/ml. Distribution of mean TNF - α vs. association was not statistically signicant (p=0.7309).Conclusion: It was found that IL10 was higher in Ascites patients though it was not statistically signicant. TNF alpha was higher in Ascites patients. TNF alpha was higher in normal Pancreatitis.

NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1

1994 ◽  
Vol 14 (10) ◽  
pp. 6561-6569
Author(s):  
L Klampfer ◽  
T H Lee ◽  
W Hsu ◽  
J Vilcek ◽  
S Chen-Kiang
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Fibroblasts ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Normal Human ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) activate transcription of the TSG-6 gene in normal human fibroblasts through a promoter region (-165 to -58) that encompasses an AP-1 and a NF-IL6 site. We show by deletion analysis and substitution mutagenesis that both sites are necessary for activation by TNF-alpha. Activation by IL-1 requires the NF-IL6 site and is enhanced by the AP-1 site. These results suggest that the NF-IL6 and AP-1 family transcription factors functionally cooperate to mediate TNF-alpha and IL-1 signals. Consistent with this possibility, IL-1 and TNF-alpha markedly increase the binding of Fos and Jun to the AP-1 site, and NF-IL6 activates the native TSG-6 promoter. Activation by NF-IL6 requires an intact NF-IL6 site and is modulated by the ratio of activator to inhibitor NF-IL6 isoforms that are translated from different in-frame AUGs. However, the inhibitor isoform can also bind to the AP-1 site and repress AP-1 site-mediated transcription. The finding that the inhibitor isoform antagonizes activation of the native TSG-6 promoter by IL-1 and TNF-alpha suggests that NF-IL6 has a physiologic role in these cytokine responses. Thus, the functionally distinct NF-IL6 isoforms cooperate with Fos and Jun to positively and negatively regulate the native TSG-6 promoter by TNF-alpha and IL-1.

Administration of tumor necrosis factor-alpha in vivo depresses endothelium-dependent relaxation

1994 ◽  
Vol 266 (6) ◽  
pp. H2535-H2541 ◽  
Author(s):  
P. Wang ◽  
Z. F. Ba ◽  
I. H. Chaudry
Keyword(s):  
Mean Arterial Pressure ◽  
Tumor Necrosis Factor ◽  
Arterial Pressure ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Vascular Relaxation ◽  
Endothelium Dependent Relaxation ◽  
Necrosis Factor

Although depressed endothelium-dependent relaxation occurs during early sepsis, the precise mechanism responsible for this remains unknown. Because the elevated levels of plasma tumor necrosis factor (TNF) play a major role in the pathophysiology of sepsis, we investigated whether TNF-alpha administration alters endothelium-dependent relaxation. To study this, recombinant TNF-alpha (1.2 x 10(7) U/mg) was infused intravenously (0.25 mg/kg body wt) for 0.5 h in normal rats, and mean arterial pressure was monitored. At 1 h after the completion of TNF-alpha or vehicle infusion, the aorta and a pulmonary artery were isolated, cut into 2.5-mm rings, and placed in organ chambers. Norepinephrine (2 x 10(-7) M) was applied to achieve near-maximal contraction, and dose responses for an endothelium-dependent vasodilator, acetylcholine, and an endothelium-independent vasodilator, nitroglycerine, were determined. In additional studies, aortic rings from normal animals were incubated with TNF-alpha for 2 h in vitro, and vascular reactivity was determined. The results indicate that TNF-alpha administration significantly reduced acetylcholine-induced vascular relaxation both in vivo and in vitro. Such a reduction was sustained at least 80 min after the completion of 2-h incubation with TNF-alpha. In contrast, TNF did not alter nitroglycerine-induced vascular relaxation. Thus TNF-alpha depresses endothelium-dependent relaxation in vitro as well as in vivo. Because TNF-alpha infusion increases plasma TNF levels without decreasing mean arterial pressure, the depressed endothelium-dependent relaxation observed during early sepsis may be due to the elevated circulating levels of TNF.

scholarly journals THE EFFICACY OF CANAKINUMAB IN THE TREATMENT OF TUMOR NECROSIS FACTOR (TNF) ALPHA RECEPTOR-ASSOCIATED PERIODIC SYNDROME (TRAPS)

2019 ◽  
Author(s):  
ERICA NAOMI NAKA MATOS ◽  
MILENA FOIZER LEITE ◽  
CAROLINA YUME ARAZAWA ◽  
QUEROLAI GOMES GADELHA ◽  
RENATO FURTADO TAVARES ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Periodic Syndrome ◽  
Necrosis Factor
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