Polymorphisms in TGFβ and TNFα Are Associated With the Myelodysplastic Syndrome Phenotype

2007 ◽  
Vol 131 (12) ◽  
pp. 1789-1793 ◽  
Author(s):  
Martin P. Powers ◽  
Ha Nishino ◽  
Yamin Luo ◽  
Alina Raza ◽  
Amulya Vanguri ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Aberrant Expression ◽  
Genotype Frequencies ◽  
Tnf Α ◽  
Genes Encoding ◽  
Primer Polymerase Chain Reaction ◽  
Factor Α ◽  
Tgf Β1 ◽  
Necrosis Factor

Abstract Context.—Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS. Objective.—To determine if certain polymorphisms in the tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) cytokines are overrepresented in a cohort of patients with MDSs. Design.—DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFα and 2 in TGFβ1, were determined using single-specific-primer polymerase chain reaction. The allele and genotype frequencies were compared with similar populations in the National Cancer Institute SNP500 database. Results.—In our MDS population, the −308A/A genotype of the TNFα gene and the TGFβ1 allele +29T and genotype +29T/T, each associated with higher levels of expression, were overrepresented in our MDS population. Conclusions.—Polymorphisms associated with increased expression in the cytokines TNFα and TGFβ1 are overrepresented in the MDS population suggesting that increased TNF-α and TGF-β1 activity may contribute to the susceptibility and/or pathogenesis of MDS. Further studies with larger sample sizes are warranted to confirm our observation.

Synergistic induction of nuclear factor-κB by transforming growth factor-β and tumour necrosis factor-α is mediated by protein kinase A-dependent RelA acetylation

2008 ◽  
Vol 417 (2) ◽  
pp. 583-591 ◽  
Author(s):  
Hajime Ishinaga ◽  
Hirofumi Jono ◽  
Jae Hyang Lim ◽  
Kensei Komatsu ◽  
Xiangbin Xu ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Tnf Α ◽  
Factor Α ◽  
Tgf Β1 ◽  
Necrosis Factor

The TGF-β (transforming growth factor-β) pathway represents an important signalling pathway involved in regulating diverse biological processes, including cell proliferation, differentiation and inflammation. Despite the critical role for TGF-β in inflammatory responses, its role in regulating NF-κB (nuclear factor-κB)-dependent inflammatory responses still remains unknown. In the present study we show that TGF-β1 synergizes with proinflammatory cytokine TNF-α (tumour necrosis factor-α) to induce NF-κB activation and the resultant inflammatory response in vitro and in vivo. TGF-β1 synergistically enhances TNF-α-induced NF-κB DNA binding activity via induction of RelA acetylation. Moreover, synergistic enhancement of TNF-α-induced RelA acetylation and DNA-binding activity by TGF-β1 is mediated by PKA (protein kinase A). Thus the present study reveals a novel role for TGF-β in inflammatory responses and provides new insight into the regulation of NF-κB by TGF-β signalling.

Exposure to febrile temperature modifies endothelial cell response to tumor necrosis factor-α

2001 ◽  
Vol 90 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Jeffrey D. Hasday ◽  
Douglas Bannerman ◽  
Sirhan Sakarya ◽  
Alan S. Cross ◽  
Ishwar S. Singh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Gm Csf ◽  
Tnf Α ◽  
Neutrophil Adherence ◽  
Endothelial Cell Response ◽  
Factor Α ◽  
Necrosis Factor

Fever is an important regulator of inflammation that modifies expression and bioactivity of cytokines, including tumor necrosis factor (TNF)-α. Pulmonary vascular endothelium is an important target of TNF-α during the systemic inflammatory response. In this study, we analyzed the effect of a febrile range temperature (39.5°C) on TNF-α-stimulated changes in endothelial barrier function, capacity for neutrophil binding and transendothelial migration (TEM), and cytokine secretion in human pulmonary artery endothelial cells (EC). Permeability for [14C]BSA tracer was increased by treatment with TNF-α, and this effect was augmented by incubating EC at 39.5°C. Treating EC with 2.5 U/ml TNF-α stimulated an increase in subsequent neutrophil adherence and TEM. Incubating EC at 39.5°C caused a 30% increase in TEM but did not modify the enhancement of neutrophil adherence or TEM by TNF-α treatment. Analysis of cytokine expression in EC cultures exposed to TNF-α at either 37° or 39.5°C revealed three patterns of temperature and TNF-α responsiveness. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8 were not detectable in untreated EC but were increased after TNF-α exposure, and this increase was enhanced at 39.5°C. IL-6 expression was also increased with TNF-α exposure, but IL-6 expression was lower in 39.5°C EC cultures. Transforming growth factor-β1was constitutively expressed, and its expression was not influenced either by TNF-α or exposure to 39.5°C. These data demonstrate that clinically relevant shifts in body temperature might cause important changes in the effects of proinflammatory cytokines on the endothelium.

scholarly journals A mechanism of suppression of TGF–β/SMAD signaling by NF-κB/RelA

2000 ◽  
Vol 14 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Markus Bitzer ◽  
Gero von Gersdorff ◽  
Dan Liang ◽  
Alfredo Dominguez-Rosales ◽  
Amer A. Beg ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Transcriptional Responses ◽  
Smad Signaling ◽  
Antisense Mrna ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

A number of pathogenic and proinflammatory stimuli, and the transforming growth factor-β (TGF-β) exert opposing activities in cellular and immune responses. Here we show that the RelA subunit of nuclear factor κB (NF-κB/RelA) is necessary for the inhibition of TGF-β-induced phosphorylation, nuclear translocation, and DNA binding of SMAD signaling complexes by tumor necrosis factor-α (TNF-α). The antagonism is mediated through up-regulation of Smad7 synthesis and induction of stable associations between ligand-activated TGF-β receptors and inhibitory Smad7. Down-regulation of endogenous Smad7 by expression of antisense mRNA releases TGF-β/SMAD-induced transcriptional responses from suppression by cytokine-activated NF-κB/RelA. Following stimulation with bacterial lipopolysaccharide (LPS), or the proinflammatory cytokines TNF-α and interleukin-1β (IL-1β, NF-κB/RelA induces Smad7 synthesis through activation of Smad7 gene transcription. These results suggest a mechanism of suppression of TGF-β/SMAD signaling by opposing stimuli mediated through the activation of inhibitory Smad7 by NF-κB/RelA.

Regulation of Murine Protein C Gene Expression In Vivo: Effects of Tumor Necrosis Factor-α, Interleukin-1, and Transforming Growth Factor-β

1999 ◽  
Vol 82 (10) ◽  
pp. 1297-1301 ◽  
Author(s):  
Takayoshi Shimokawa ◽  
Tetsuhito Kojima ◽  
David Loskutoff ◽  
Hidehiko Saito ◽  
Koji Yamamoto
Keyword(s):  
Growth Factor ◽  
Protein C ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Transforming Growth Factor Β ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

SummaryProtein C is a precursor of the anticoagulant serine protease, activated protein C, which inhibits coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C synthesis, we previously demonstrated that the kidney and male reproductive organs also expressed abundant protein C mRNA in the mouse. In the present study, we further investigated the effects of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and transforming growth factor-β (TGF-β) on the expression of protein C mRNA in the principal producing organs, i.e., the liver, kidney, and testis. Both quantitative reverse transcription-PCR assay and in situ hybridization analysis revealed that TNF-α decreased protein C mRNA expression in the liver, kidney, and testis. IL-1 also down-regulated protein C mRNA expression in the liver and testis, but not in the kidney. In contrast, TGF-β unchanged the expression level of protein C mRNA in these three organs. These observations suggest that TNF-α and IL-1 may contribute to an increase in the procoagulant potential by down-regulation of protein C synthesis in the tissues during inflammatory processes.

scholarly journals Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

2014 ◽  
Vol 15 (6) ◽  
pp. 746-749 ◽  
Author(s):  
Faezeh Khozeimeh ◽  
Omid Savabi ◽  
Masih Esnaashari
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Transforming Growth Factor ◽  
Pemphigus Vulgaris ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Tnf Α ◽  
Interleukin 1Α ◽  
Factor Α ◽  
Necrosis Factor

ABSTRACT Pemphigus is an autoimmune blistering disease characterized by a loss of cell adhesion result in acantholysis. Genetic factors and immunologic factors such as cytokines particularly IL-1α, IL-10, TNF-α, and TGF-β may counterpart to developing of Pemphigus. The aim of this study was to evaluate. The concentration of IL-1α, IL-10, TNF-α, TGF-α in serum of pemphigus vulgaris (PV) patients and normal individuals. Material and methods In this analytic and descriptive study 25 patients with pemphigus vulgaris (in active phase) and 25 healthy persons were examined. Serum samples of two groups were obtained and the level of IL-1α, IL-10, TNF-α and TGF-β were measured by ELISA technique. The data were analyzed statistically by independent T test (α = 0/05). Results All cytokines tested, showed higher concentration in patient's sera comparing to healthy control individuals. The level of IL-1α (p = 0.004), TNF-α (p = 0.008) and TGF-β (p = 0.009) were statistically different in two experimental groups, There was no significant difference in IL-10 level (p = 0.605). Conclusion Cytokines such as IL-1α, IL-10, TNF-α and TGF-β probably have a role in pathogenesis of PV. Further comprehensive studies are suggested to confirm these findings. How to cite this article Khozeimeh F, Savabi O, Esnaashari M. Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris. J Contemp Dent Pract 2014;15(6):746-749.

scholarly journals The Effect of Azadirachta indica leaves extract on Transforming Growth Factor-β and Tumor Necrosis Factor-α in a Plasmodium berghei infected Mice model

2021 ◽  
Vol 7 (1) ◽  
pp. 42
Author(s):  
Zainabur Rahmah
Keyword(s):  
Azadirachta Indica ◽  
Plasmodium Berghei ◽  
Tumor Necrosis ◽  
Leaf Extract ◽  
Tumor Necrosis Factor Α ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Malaria is a health problem for the world's population and is predominantly located in tropical and subtropical areas. The three countries with the most malaria cases are India (58%), followed by Indonesia (20%), then Myanmar (16%). This study aims to determine the effect of neem leaf extract on increasing TGF-β expression and decreasing TNF-α expression in mice infected with Plasmodium berghei. In this study there were four groups, namely Treatment 1 (in Plasmodium berghei infection without therapy). Treatment 2 (in Plasmodium berghei infection and treated with Azadirachta indica leaf extract at a dose of 0.25 mg / g BW). Treatment 3 = (in Plasmodium berghei infection and therapy with Azadirachta indica leaves at a dose of 0.5 mg / g BW). Treatment 4 = (in Plasmodium berghei infection and treated with Azadirachta indica leaves at a dose of 1 mg / g BW). TGF-β examination by elisa method and TNF-α by immunohistochemistry. Data analysis using SEM (Structural Equation Modeling) The results of treatment 1 and 2 showed a decrease in plasma TGF-β expression (t = 1.13; tcount = 1.93; ≥ttabel = 1.96) and spleen (tcount = 1.53; tcount = 1.45; ≥ttabel = 1.96) but there was an increase in spleen TNF-α expression (tcount = 1.77; tcount = 1.00; ≥ttabel = 1.96). Groups 3 and 4 showed an increase in plasma TGF-β expression (tcount = 5.13; tcount = 2.42; ≥ttable = 1.96) and spleen (tcount = 2.00; tcount = 1.97; ≥ttabel = 1.96) but there was a decrease in spleen TNF-α expression (tcount = 2.03; tcount = 2.11; ≥ttabel = 1.96). Conclusion: Azadirachta indica leaf therapy can increase TGF-β expression and decrease TNF-α expression in the spleen. Keywords: Azadirachta indica ethanol extract, transforming growth factor- β, tumor necrosis factor-α

scholarly journals The Effects of Rice Husk Liquid Smoke in Porphyromonas gingivalis-Induced Periodontitis

2021 ◽  
Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah
Keyword(s):  
Growth Factor ◽  
Porphyromonas Gingivalis ◽  
Rice Husk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Proliferation Markers ◽  
Liquid Smoke ◽  
Tnf Α ◽  
Factor Α

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.

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