Epidermal growth factor, tumor necrosis factor alpha, and thioredoxin in cerebral tissue following cerebral ischemia / Serebral iskemi sonrası beyin dokusunda epidermal büyüme faktörü, tümör nekrozis faktör alfa ve tiyoredoksin

2015 ◽  
Vol 40 (6) ◽  
Author(s):  
Hatice Ferhan Kömürcü ◽  
Nedret Kılıç ◽  
Melike Erol Demirbilek ◽  
Serdar Kahraman
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cerebral Tissue ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Epidermal Growth ◽  
Factor Alpha ◽  
Necrosis Factor

AbstractObjective: In this study, the changes in the levels of the epidermal growth factor (EGF), tumor necrosis factor alpha (TNF-α), and thioredoxine (TRX) in the cerebral tissue of rats following the cerebral ischemia model were investigated.Methods: The left middle cerebral artery occlusion (MCAO) was done in 27 out of 48 rats recruited into the study for obtaining focal cerebral ischemia model (MCAO group). Twenty-one rats underwent a sham operation; the middle cerebral artery was exposed but not occluded (Sham group). EGF, TNF-α, and TRX levels were studied in the operated left and contralateral hemispheres at the 16Results: EGF levels at 96Conclusion: The results suggested that cerebral ischemia following MCAO might affect EGF, TNF-α and TRX levels in both ischemic and contralateral hemispheres in cerebral tissue; and this effect may change by the time passed after MCAO.

scholarly journals Inhibition of Mycobacterium bovisBCG-Induced Tumor Necrosis Factor Alpha Secretion in Human Cells by Transforming Growth Factor β

1998 ◽  
Vol 5 (4) ◽  
pp. 588-591 ◽  
Author(s):  
Patricia Méndez-Samperio ◽  
Marisol Hernandez-Garay ◽  
Angela Nuñez Vazquez
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The effect of exogenous transforming growth factor β (TGF-β) onMycobacterium bovis BCG-induced tumor necrosis factor alpha (TNF-α) production by human mononuclear cells was studied. It was found that TNF-α production by human cells stimulated with BCG was significantly inhibited by TGF-β. The specificity of the observed inhibition was demonstrated, since the addition of an anti-TGF-β neutralizing monoclonal antibody completely reversed the inhibitory effect. Furthermore, the suppressive effect of TGF-β on TNF-α secretion in this system was not due to a direct cytotoxic effect, since cell viability was comparable in the presence or absence of TGF-β. Interestingly, our results demonstrated comparative suppressive effects of TGF-β and interleukin-10 on BCG-induced TNF-α secretion. Together, the data demonstrate, for the first time, that TGF-β inhibits BCG-induced TNF-α secretion by human cells.

Substitution of methionine 435 with leucine, isoleucine, and serine in tumor necrosis factor alpha converting enzyme inactivates ectodomain shedding activity

2007 ◽  
Vol 85 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Liliana Pérez ◽  
John E. Kerrigan ◽  
Xiaojin Li ◽  
Huizhou Fan
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-α) converting enzyme (TACE) is a zinc metalloprotease that has emerged as a general sheddase, which is responsible for ectodomain release of numerous membrane proteins, including the proinflammatory cytokine TNF-α, the leukocyte adhesin l-selectin and epidermal growth factor receptor ligand-transforming growth factor α (TGF-α), and related family members. Structurally, TACE belongs to a large clan of proteases, designated the metzincins, because TACE possesses a conserved methionine (Met435), frequently referred to as the met-turn residue, in its active site. A vital role of this residue in the function of TACE is supported by the fact that cells expressing the M435I TACE variant are defective in ectodomain shedding. However, the importance of Met435 in TACE appears to be uncertain, since another metzincin, matrix metalloprotease-2, has been found to be enzymatically fully active with either leucine or serine in place of its met-turn residue. We constructed TACE mutants with leucine or serine in place of Met435 to further examine the role of the met-turn residue in TACE-mediated ectodomain cleavage. Similar to the M435I TACE mutant, both the M435L and M435S constructs are defective in cleaving transmembrane TNF-α, TGF-α, and l-selectin. Comparative modeling and dynamic computation detected structural perturbations, which resulted in higher energy, in the catalytic zinc complexes of the Met435 TACE mutants compared with that in the wild-type enzyme. Thus, Met435 serves to maintain the stability of the catalytic center of TACE for the hydrolysis of peptide bonds in substrates.

scholarly journals Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

2015 ◽  
Vol 35 (21) ◽  
pp. 3604-3621 ◽  
Author(s):  
Yongjia Feng ◽  
Yu-Hwai Tsai ◽  
Weidong Xiao ◽  
Matthew W. Ralls ◽  
Alex Stoeck ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Necrosis Factor Alpha ◽  
Mucosal Atrophy ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Total parenteral nutrition (TPN) is commonly used clinically to sustain patients; however, TPN is associated with profound mucosal atrophy, which may adversely affect clinical outcomes. Using a mouse TPN model, removing enteral nutrition leads to decreased crypt proliferation, increased intestinal epithelial cell (IEC) apoptosis and increased mucosal tumor necrosis factor alpha (TNF-α) expression that ultimately produces mucosal atrophy. Upregulation of TNF-α signaling plays a central role in mediating TPN-induced mucosal atrophy without intact epidermal growth factor receptor (EGFR) signaling. Currently, the mechanism and the tissue-specific contributions of TNF-α signaling to TPN-induced mucosal atrophy remain unclear. ADAM17 is an ectodomain sheddase that can modulate the signaling activity of several cytokine/growth factor receptor families, including the TNF-α/TNF receptor and ErbB ligand/EGFR pathways. Using TPN-treated IEC-specific ADAM17-deficient mice, the present study demonstrates that a loss of soluble TNF-α signaling from IECs attenuates TPN-induced mucosal atrophy. Importantly, this response remains dependent on the maintenance of functional EGFR signaling in IECs. TNF-α blockade in wild-type mice receiving TPN confirmed that soluble TNF-α signaling is responsible for downregulation of EGFR signaling in IECs. These results demonstrate that ADAM17-mediated TNF-α signaling from IECs has a significant role in the development of the proinflammatory state and mucosal atrophy observed in TPN-treated mice.

scholarly journals Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

2016 ◽  
Vol 24 (3) ◽  
pp. 307-317
Author(s):  
Melike Erol-Demirbilek ◽  
Nedret Kilic ◽  
Hatice Ferhan Komurcu
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Epidermal Growth Factor ◽  
Tumor Necrosis ◽  
Tnf Α ◽  
Thioredoxin System ◽  
Epidermal Growth ◽  
Cerebral Ischemic ◽  
Necrosis Factor

Abstract Background: Thioredoxin reductase (TrxR), epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains. Methods: Sprague-Dawley rats divided into three groups. Rats in control group were not subjected to any of treatments and their brains were removed under anesthesia. Middle cerebral arters were exposed but not occluded for the sham-operated rats. Animals were subjected to permanent middle cerebral arter occlusion (MCAO) in MCAO-operated group. The rats were decapitated at 16 hours (h), 48 h and 96 h after sham operation and focal cerebral ischemia. TrxR activities, EGF and TNF-α levels were measured in ischemic and non-ischemic hemispheres for all groups. Results: In group MCAO, TrxR activities were significantly low at 48 h in ischemic hemisphere in comparison to control. After the 48 h, a remarkable increase was observed at 96 h. EGF and TNF-α levels were substantially high at 96 h in group MCAO of ischemic brain. Conclusion: TrxR activity was reduced by oxidative stress which was formed by ischemia. EGF levels increased to exhibit neurotrophic and neuroprotective effects. After ischemia, TNF-α levels increased as a response to the tissue damage. Further studies with a higher number of experimental subjects and shorter or longer periods such as from first 30 minutes up to 3 months may be more informative to show the time-dependent variations in TrxR, EGF and TNF-α in cerebral ischemic injury.

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