Host response to cytoadherence in Plasmodium falciparum

2008 ◽  
Vol 36 (2) ◽  
pp. 221-228 ◽  
Author(s):  
Srabasti J. Chakravorty ◽  
Katie R. Hughes ◽  
Alister G. Craig
Keyword(s):  
Plasmodium Falciparum ◽  
Tumour Necrosis ◽  
Host Response ◽  
Severe Disease ◽  
Signalling Pathways ◽  
Malarial Infection ◽  
Extensive Information ◽  
Adhesive Interactions ◽  
Necrosis Factor ◽  
Tnf Tumour Necrosis Factor

Cytoadherence of PRBCs (Plasmodium falciparum-infected red blood cells) to host endothelium has been associated with pathology in severe malaria, but, despite extensive information on the primary processes involved in the adhesive interactions, the mechanisms underlying the disease are poorly understood. Endothelial cells have the ability to mobilize immune and pro-adhesive responses when exposed to both PRBCs and TNF (tumour necrosis factor). In addition, there is also an up-regulation by PRBCs and TNF and a concurrent down-regulation of a range of genes involved in inflammation and cell death, by PRBCs and TNF. We propose that the balance between positive and negative regulation will contribute to endothelial pathology during malarial infection. Apposition of PRBCs has been shown by a number of groups to activate signalling pathways. This is dependent, at least in part, on the cytoadherence characteristics of the invading isolate, such that the avidity of the PRBC for the receptor on host endothelium is proportional to the level of activation of the signalling pathways. An understanding of the post-adhesive processes produced by cytoadherence may help us to understand the variable pathology seen in malaria and to design appropriate therapies to alleviate severe disease.

scholarly journals Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1221
Author(s):  
Alvaro Martinez Mesa ◽  
Eva Cabrera César ◽  
Elisa Martín-Montañez ◽  
Esther Sanchez Alvarez ◽  
Pilar Martinez Lopez ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lactate Dehydrogenase ◽  
Lung Injury ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Severe Disease ◽  
Discriminative Ability ◽  
Total Thiol ◽  
Effective Manner ◽  
Necrosis Factor

Introduction: SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). Method: 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. Results: C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. Conclusion: In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.

scholarly journals Tumour necrosis factor induces phosphorylation primarily of the nitric-oxide-responsive form of glyoxalase I

2007 ◽  
Vol 407 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Virginie de Hemptinne ◽  
Dieter Rondas ◽  
Joël Vandekerckhove ◽  
Katia Vancompernolle
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
No Synthase ◽  
Dominant Factor ◽  
Glyoxalase I ◽  
No Donor ◽  
Necrosis Factor ◽  
Tnf Tumour Necrosis Factor

We have previously shown that TNF (tumour necrosis factor) induces phosphorylation of GLO1 (glyoxalase I), which is required for cell death in L929 cells. In the present paper, we show that the TNF-induced phosphorylation of GLO1 occurs primarily on the NO (nitric oxide)-responsive form of GLO1. In addition, analysis of several cysteine mutants of GLO1 indicated that Cys-138, in combination with either Cys-18 or Cys-19, is a crucial target residue for the NO-mediated modification of GLO1. Furthermore, the NO-donor GSNO (S-nitrosogluthathione) induces NO-mediated modification of GLO1 and enhances the TNF-induced phosphorylation of this NO-responsive form. GSNO also strongly promotes TNF-induced cell death. By the use of pharmacological inhibition of iNOS (inducible NO synthase) and overexpression of mutants of GLO1 that are deficient for the NO-mediated modification, we have shown that the NO-mediated modification of GLO1 is not a requirement for TNF-induced phosphorylation or TNF-induced cell death respectively. In summary, these data suggest that the TNF-induced phosphorylation of GLO1 is the dominant factor for cell death.

scholarly journals Transcriptional Reprogramming and Constitutive PD-L1 Expression in Melanoma Are Associated with Dedifferentiation and Activation of Interferon and Tumour Necrosis Factor Signalling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4250
Author(s):  
Antonio Ahn ◽  
Euan J. Rodger ◽  
Jyoti Motwani ◽  
Gregory Gimenez ◽  
Peter A. Stockwell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Targeted Therapy ◽  
Tumour Necrosis Factor ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Tumour Necrosis ◽  
Melanoma Cells ◽  
Signalling Pathways ◽  
Necrosis Factor ◽  
Melanoma Cell Lines

Melanoma is the most aggressive type of skin cancer, with increasing incidence worldwide. Advances in targeted therapy and immunotherapy have improved the survival of melanoma patients experiencing recurrent disease, but unfortunately treatment resistance frequently reduces patient survival. Resistance to targeted therapy is associated with transcriptomic changes and has also been shown to be accompanied by increased expression of programmed death ligand 1 (PD-L1), a potent inhibitor of immune response. Intrinsic upregulation of PD-L1 is associated with genome-wide DNA hypomethylation and widespread alterations in gene expression in melanoma cell lines. However, an in-depth analysis of the transcriptomic landscape of melanoma cells with intrinsically upregulated PD-L1 expression is lacking. To determine the transcriptomic landscape of intrinsically upregulated PD-L1 expression in melanoma, we investigated transcriptomes in melanomas with constitutive versus inducible PD-L1 expression (referred to as PD-L1CON and PD-L1IND). RNA-Seq analysis was performed on seven PD-L1CON melanoma cell lines and ten melanoma cell lines with low inducible PD-L1IND expression. We observed that PD-L1CON melanoma cells had a reprogrammed transcriptome with a characteristic pattern of dedifferentiated gene expression, together with active interferon (IFN) and tumour necrosis factor (TNF) signalling pathways. Furthermore, we identified key transcription factors that were also differentially expressed in PD-L1CON versus PD-L1IND melanoma cell lines. Overall, our studies describe transcriptomic reprogramming of melanomas with PD-L1CON expression.

scholarly journals ADAM17-triggered TNF signalling protects the ageing Drosophila retina from lipid droplet mediated degeneration

2020 ◽  
Author(s):  
Sonia Muliyil ◽  
Clémence Levet ◽  
Stefan Düsterhöft ◽  
Iqbal Dulloo ◽  
Sally Cowley ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Tumour Necrosis ◽  
Later Life ◽  
Cellular Damage ◽  
Oxygen Species ◽  
Tnf Receptor ◽  
Age Related ◽  
Abnormal Accumulation ◽  
Necrosis Factor ◽  
Tnf Tumour Necrosis Factor

AbstractAnimals have evolved multiple mechanisms to protect themselves from the cumulative effects of age-related cellular damage. Here we reveal an unexpected link between the TNF (tumour necrosis factor) inflammatory pathway, triggered by the metalloprotease ADAM17/TACE, and a lipid droplet (LD)-mediated mechanism of protecting retinal cells from age related degeneration. Loss of ADAM17, TNF and the TNF receptor Grindelwald in pigmented glial cells of the Drosophila retina leads to age related degeneration of both glia and neurons, preceded by an abnormal accumulation of glial LDs. We show that the glial LDs initially buffer the cells against damage caused by neuronally generated reactive oxygen species (ROS), but that in later life the LDs dissipate, leading to the release of toxic peroxidated lipids. Finally, we demonstrate the existence of a conserved pathway in human iPS-derived microglia-like cells, which are central players in neurodegeneration. Overall, we have discovered a pathway mediated by TNF signalling acting not as a trigger of inflammation, but as a cytoprotective factor in the retina.

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