Biocompatibility Reduces Inflammation-Induced Apoptosis in Mesothelial Cells Exposed to Peritoneal Dialysis Fluid

2015 ◽  
Vol 39 (1-3) ◽  
pp. 200-209 ◽  
Author(s):  
Beatriz Santamaría ◽  
Alvaro Conrado Ucero ◽  
Alberto Benito-Martin ◽  
Maria Jesús Vicent ◽  
Mar Orzáez ◽  
...  
Keyword(s):  
Cell Death ◽  
Peritoneal Dialysis ◽  
Inflammatory Cytokines ◽  
Mesothelial Cell ◽  
Major Complication ◽  
Interferon Γ ◽  
Mesothelial Cells ◽  
Tnf Α ◽  
Peritoneal Dialysis Fluid ◽  
Induced Apoptosis

Background/Aims: Peritonitis is a major complication that arises out of peritoneal dialysis (PD), leading to death and loss of mesothelium and peritoneal injury, which may impede PD. We studied the combined impact of inflammatory mediators and PD fluids on mesothelial cell death. Methods: Cultured human mesothelial cells. Results: Inflammatory cytokines (TNF-α and interferon-γ) cooperate with bioincompatible PD fluids containing high glucose degradation product (GDP) concentrations to promote mesothelial cell death. Thus, the inflammatory cytokine cocktail induced a higher rate of death in cells cultured in high GDP PD fluid than in low GDP PD fluid or cell culture medium (cell death expressed as % hypodiploid cells: TNF-α and interferon-γ in RPMI: 14.15 ± 1.68, TNF-α and interferon-γ in 4.25% low GDP PD fluid 13.16 ± 3.29, TNF-α and interferon-γ in 4.25% high GDP PD fluid 25.88 ± 2.18%, p < 0.05 vs. the other two groups). BclxL BH4 peptides, Apaf-1 inhibition or caspase inhibition failed to protect from apoptosis induced by the combination of inflammatory cytokines and bioincompatible PD fluids, although they protected from other forms of mesothelial cell apoptosis. Conclusion: Inflammation cooperates with high GDP PD fluids to promote mesothelial cell death, which is resistant to several therapeutic approaches. This information provides a framework for selection of PD fluid during peritonitis.

scholarly journals A Novel Formulation of Glucose-Sparing Peritoneal Dialysis Solutions with l-Carnitine Improves Biocompatibility on Human Mesothelial Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 123
Author(s):  
Francesca Piccapane ◽  
Mario Bonomini ◽  
Giuseppe Castellano ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Mesothelial Cells ◽  
Apical Side ◽  
New Formulation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Dialysis Solutions ◽  
Pro Inflammatory Cytokines

The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.

scholarly journals Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced by Vibrio cholerae

Toxins ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 12
Author(s):  
Kohei Ogura ◽  
Kinnosuke Yahiro ◽  
Joel Moss
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Vibrio Cholerae ◽  
Elongation Factor ◽  
Host Cells ◽  
Mitogen Activated Protein Kinase ◽  
Pseudomonas Exotoxin A ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Adp Ribosyltransferase

Pathogenic microorganisms produce various virulence factors, e.g., enzymes, cytotoxins, effectors, which trigger development of pathologies in infectious diseases. Cholera toxin (CT) produced by O1 and O139 serotypes of Vibrio cholerae (V. cholerae) is a major cytotoxin causing severe diarrhea. Cholix cytotoxin (Cholix) was identified as a novel eukaryotic elongation factor 2 (eEF2) adenosine-diphosphate (ADP)-ribosyltransferase produced mainly in non-O1/non-O139 V. cholerae. The function and role of Cholix in infectious disease caused by V. cholerae remain unknown. The crystal structure of Cholix is similar to Pseudomonas exotoxin A (PEA) which is composed of an N-terminal receptor-recognition domain and a C-terminal ADP-ribosyltransferase domain. The endocytosed Cholix catalyzes ADP-ribosylation of eEF2 in host cells and inhibits protein synthesis, resulting in cell death. In a mouse model, Cholix caused lethality with severe liver damage. In this review, we describe the mechanism underlying Cholix-induced cytotoxicity. Cholix-induced apoptosis was regulated by mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways, which dramatically enhanced tumor necrosis factor-α (TNF-α) production in human liver, as well as the amount of epithelial-like HepG2 cancer cells. In contrast, Cholix induced apoptosis in hepatocytes through a mitochondrial-dependent pathway, which was not stimulated by TNF-α. These findings suggest that sensitivity to Cholix depends on the target cell. A substantial amount of information on PEA is provided in order to compare/contrast this well-characterized mono-ADP-ribosyltransferase (mART) with Cholix.

Continuous Mesothelial Injury and Regeneration during long Term Peritoneal Dialysis

1987 ◽  
Vol 7 (3) ◽  
pp. 148-156 ◽  
Author(s):  
Lazaro Gotloib ◽  
Abshalom Shostack ◽  
Phina Bar-Sella ◽  
Ricardo Cohen
Keyword(s):  
Peritoneal Dialysis ◽  
Connective Tissue ◽  
Peritoneal Fluid ◽  
Mesothelial Cell ◽  
Mesothelial Cells

This study reconstructs the whole sequence of mesothelial injury and regeneration in patients on longterm peritoneal dialysis. Our observations indicate that peritoneal dialysis induces a process of continuous mesothelial injury and regeneration. New mesothelial cells seem to originate from wandering mesothelial cells of the peritoneal fluid, as well as from mesothelial cell precursors localized in the sub-mesothelial connective tissue.

Interferon-γ rescues TNF-α-induced apoptosis mediated by up-regulation of TNFR2 on EoL-1 cells

1999 ◽  
Vol 27 (3) ◽  
pp. 512-519 ◽  
Author(s):  
Takeo Horie ◽  
Kunio Dobashi ◽  
Kunihiko Iizuka ◽  
Akihiro Yoshii ◽  
Yasuo Shimizu ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Tnf Α ◽  
Induced Apoptosis

Cancer Antigen 1251S Locally Produced in the Peritoneal Cavity during Continuous Ambulatory Peritoneal Dialysis

1994 ◽  
Vol 14 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Ger C.M. Koomen ◽  
Michiel G.H. Betjes ◽  
Oésirée Zemel ◽  
Raymond T. Krediet ◽  
Frans J. Hoek
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Mesothelial Cell ◽  
Linear Increase ◽  
Mesothelial Cells ◽  
Ca 125 ◽  
Cancer Antigen ◽  
The Relationship

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10 23), dialysate CA 125 18 U/mL (range 5.2 76), dialysate/plasma ratio 1. 9 (range 0.61 -5.4), and number of mesothelial cells 400/mL (range 10 5000). Peritoneal concentrations of mesothelial cellsand CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/1 06 cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

scholarly journals Tumor Necrosis Factor-α Attenuates Thyroid Hormone-Induced Apoptosis in Vascular Endothelial Cell Line XLgoo Established from Xenopus Tadpole Tails

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3379-3389 ◽  
Author(s):  
Shuuji Mawaribuchi ◽  
Kei Tamura ◽  
Saori Okano ◽  
Shutaro Takayama ◽  
Yoshio Yaoita ◽  
...  
Keyword(s):  
Cell Death ◽  
Thyroid Hormone ◽  
Cell Fate ◽  
Thyroid Hormone Receptor ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
Survival Signaling ◽  
Induced Apoptosis ◽  
Thyroid Hormone Receptor Β

Amphibian metamorphosis induced by T3 involves programmed cell death and the differentiation of various types of cells in degenerated and reconstructed tissues. However, the signaling pathway that directs the T3-dependent cell-fate determinations remains unclear. TNF-α is a pleiotropic cytokine that affects diverse cellular responses. Engagement of TNF-α with its receptor (TNFR1) causes intracellular apoptotic and/or survival signaling. To investigate TNF signaling functions during anuran metamorphosis, we first identified Xenopus laevis orthologs of TNF (xTNF)-α and its receptor. We found that xTNF-α activated nuclear factor-κB in X. laevis A6 cells through the Fas-associated death domain and receptor-interacting protein 1. Interestingly, xTNF-α mRNA in blood cells showed prominent expression at prometamorphosis during metamorphosis. Next, to elucidate the apoptotic and/or survival signaling induced by xTNF-α in an in vitro model of metamorphosis, we established a vascular endothelial cell line, XLgoo, from X. laevis tadpole tail. XLgoo cells formed actin stress fibers and elongated in response to xTNF-α. T3 induced apoptosis in these cells, but the addition of xTNF-α blocked the T3-induced apoptosis. In addition, treatment of the cells with T3 for 2 d induced the expression of thyroid hormone receptor-β and caspase-3, and this thyroid hormone receptor-β induction was drastically repressed by xTNF-α. Furthermore, in organ culture of the tail, xTNF-α significantly attenuated the tail degeneration induced by T3. These findings suggested that xTNF-α could protect vascular endothelial cells from apoptotic cell death induced by T3 during metamorphosis and thereby participate in the regulation of cell fate.

Glucose-Free Dialysis Solutions: Inductors of Inflammation or Preservers of Peritoneal Membrane?

2005 ◽  
Vol 25 (5) ◽  
pp. 453-460 ◽  
Author(s):  
Terhi A. Martikainen ◽  
Anna-Maija Teppo ◽  
Carola Grönhagen–Riska ◽  
Agneta V. Ekstrand
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Mass ◽  
Mesothelial Cell ◽  
University Hospital ◽  
Intercellular Adhesion Molecule ◽  
Peritoneal Membrane ◽  
Cancer Antigen 125 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Dialysis Solutions

Objectives Glucose and other bioincompatible factors of conventional peritoneal dialysis solutions may damage the peritoneal membrane. The aim of our study was to investigate whether replacement of glucose with icodextrin (ID) or amino acids (AA) affects inflammatory parameters or cancer antigen 125 (CA125). Design Either ID or AA was used, in random order, in one daily exchange during an 8-week period. After the first study period, the patients entered a washout period and then switched to the other study solution for an 8-week period. C-reactive protein (CRP) was measured in serum, and CA125, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), and hyaluronan (HA) were measured in the overnight dwell dialysates at the beginning and end of the study periods. Setting A university hospital. Patients 22 patients with duration on peritoneal dialysis of 1.5 – 6.3 months. Main Outcome Measures Levels of serum CRP and dialysate CA125, IL-6, HA, and sICAM-1 during use of ID and AA were compared to levels during use of glucose-only-based solutions. Results CRP increased significantly during use of ID. CA125 increased significantly during 8 weeks’ use of AA, from 22.8 (5.4 – 89.0) to 42.9 (7.1 – 92.9) kU/L ( p = 0.007). IL-6 increased during 8 weeks’ use of AA, from 22.0 (9.0 – 108.0) to 36.5 (14.0 – 93.0) ng/L ( p = 0.002) and ID, from 25.5 (8.0 – 82.0) to 40.0 (12.0 – 118.0) ng/L ( p = 0.008). TNF-α also increased significantly during use of ID, but showed no significant changes during use of AA. Conclusions The use of glucose-free solutions, especially AA, may lead to preservation of mesothelial cell mass and host defense. However, activation of systemic and peritoneal inflammation may appear during the use of ID and to a lesser extent during use of AA.

Tumor necrosis factor-α and ceramide induce cell death through different mechanisms in rat mesangial cells

1999 ◽  
Vol 276 (3) ◽  
pp. F390-F397 ◽  
Author(s):  
Yan-Lin Guo ◽  
Baobin Kang ◽  
Li-Jun Yang ◽  
John R. Williamson
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mesangial Cells ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

It has been proposed that ceramide acts as a cellular messenger to mediate tumor necrosis factor-α (TNF-α)-induced apoptosis. Based on this hypothesis, it was postulated that resistance of some cells to TNF-α cytotoxicity was due to an insufficient production of ceramide on stimulation by TNF-α. The present study was initiated to investigate whether this was the case in mesangial cells, which normally are insensitive to TNF-α-induced apoptosis. Our results indicate that although C2ceramide was toxic to mesangial cells, the cell death it induced differed both morphologically and biochemically from that induced by TNF-α in the presence of cycloheximide (CHX). The most apparent effect of C2ceramide was to cause cells to swell, followed by disruption of the cell membrane. It is evident that C2ceramide caused cell death by necrosis, whereas TNF-α in the presence of CHX killed the cells by apoptosis. C2ceramide did not mimic the effects of TNF-α on the activation of c-Jun NH2-terminal protein kinase and nuclear factor-κB transcription factor. Although mitogen-activated protein kinase [extracellular signal-related kinase (ERK)] was activated by both C2ceramide and TNF-α, such activation appeared to be mediated by different mechanisms as judged from the kinetics of ERK activation. Furthermore, the cleavage of cytosolic phospholipase A2during cell death induced by C2ceramide and by TNF-α in the presence of CHX showed distinctive patterns. The present study provides evidence that apoptosis and necrosis use distinctive signaling machinery to cause cell death.

Overnight Mesothelial Cell Exfoliation: A Magic Tool for Predicting Future Ultrafiltration Failure in Patients on Continuous Ambulatory Peritoneal Dialysis

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 107-113
Author(s):  
Talerngsak Kanjanabuch ◽  
Monchai Siribamrungwong ◽  
Rungrote Khunprakant ◽  
Sirigul Kanjanabuch ◽  
Piyathida Jeungsmarn ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Nutrition Status ◽  
Continuous Exposure ◽  
Peritoneal Membrane ◽  
Dialysis Solution ◽  
Ultrafiltration Failure

⋄ Background Continuous exposure of the peritoneal membrane to dialysis solutions during long-term dialysis results in mesothelial cell loss, peritoneal membrane damage, and thereby, ultrafiltration (UF) failure, a major determinant of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, none of tests available today can predict long-term UF decline. Here, we propose a new tool to predict such a change. ⋄ Mesothelial cells from 8-hour overnight effluents (1.36% glucose dialysis solution) were harvested, co-stained with cytokeratin (a mesothelial marker) and TUNEL (an apoptotic marker), and were counted using flow cytometry in 48 patients recently started on CAPD. Adequacy of dialysis, UF, nutrition status, dialysate cancer antigen 125 (CA125), and a peritoneal equilibration test (3.86% glucose peritoneal dialysis solution) were simultaneously assessed and were reevaluated 1 year later. ⋄ Results The numbers of total and apoptotic mesothelial cells were 0.19 ± 0.19 million and 0.08 ± 0.12 million cells per bag, respectively. Both numbers correlated well with the levels of end dialysate–to–initial dialysate (D/D0) glucose, dialysate-to-plasma (D/P) creatinine, and sodium dipping. Notably, the counts of cells of both types in patients with diabetes or with high or high-average transport were significantly greater than the equivalent counts in nondiabetic patients or those with low or low-average transport. A cutoff of 0.06 million total mesothelial cells per bag had sensitivity of 1 and a specificity of 0.75 in predicting a further decline in D/D0 glucose and a sensitivity of 0.86 and a specificity of 0.63 to predict a further decline in UF over a 1-year period. In contrast, dialysate CA125 and other measured parameters had low predictive values. ⋄ Conclusions The greater the loss of exfoliated cells, the worse the expected decline in UF. The ability of a count of mesothelial cells to predict a future decline in UF warrants further investigation in clinical practice.

Impairment of MCP-1 Expression in Mesothelial Cells Exposed to Peritoneal Dialysis Fluid by Osmotic Stress and Acidic Stress

2011 ◽  
Vol 31 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Ryouji Ogata ◽  
Nobuhiko Hiramatsu ◽  
Kunihiro Hayakawa ◽  
Shotaro Nakajima ◽  
Jian Yao ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Osmotic Stress ◽  
Map Kinase ◽  
Mesothelial Cells ◽  
P38 Map Kinase ◽  
Low Ph ◽  
Acidic Stress ◽  
Dialysis Fluid ◽  
Map Kinase Phosphatase ◽  
Peritoneal Dialysis Fluid

BackgroundBacterial peritonitis is one of the most frequent complications in patients on peritoneal dialysis. In the present study, we investigated effects of peritoneal dialysis fluid (PDF) on mesothelial cell recruitment of macrophages, focusing especially on unphysiological properties of PDF.MethodsHuman and murine mesothelial cells were exposed to PDF or individual properties of PDF (low pH, high glucose concentration, hyperosmolality, high lactate concentration) in vitro and in vivo, treated with inflammatory stimuli, and subjected to analyses of monocyte chemo-attractant protein-1 (MCP-1), nuclear factor-κB (NF-κB), mitogen-activated protein (MAP) kinases, and MAP kinase phosphatase-1 (MKP-1).ResultsWe found that intraperitoneal administration of PDF suppressed expression of MCP-1 and infiltration of mononuclear cells in the peritoneum of mice following injection with lipopolysaccharide. Among the unphysiological properties of PDF, low pH and hyperosmolality caused blunted induction of MCP-1 in cytokine-stimulated mesothelial cells. The attenuated response was ascribed to suppression of NF-κB by low pH and inhibition of p38 MAP kinase by hyperosmolality. Furthermore, the attenuated phosphorylation of p38 MAP kinase by osmotic stress was associated with induction of MKP-1.ConclusionThese results suggest a possibility that mesothelial cells exposed to PDF exhibit attenuated MCP-1 expression and consequent impairment of macrophage recruitment through dual mechanisms, that is, inhibition of NF-κB by acidic stress and blunted activation of p38 MAP kinase by osmotic stress. In patients on peritoneal dialysis, blunted expression of chemokines may lead to perturbation of bacterial clearance by macrophages in the peritoneal cavity.

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