scholarly journals Peritoneal dialysis fluids can alter HSP expression in human peritoneal mesothelial cells

2010 ◽  
Vol 26 (3) ◽  
pp. 1046-1052 ◽  
Author(s):  
T. O. Bender ◽  
M. Bohm ◽  
K. Kratochwill ◽  
R. Vargha ◽  
A. Riesenhuber ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Dialysis Fluids

scholarly journals Glucose-Based Peritoneal Dialysis Fluids Downregulate Toll-Like Receptors and Trigger Hyporesponsiveness to Pathogen-Associated Molecular Patterns in Human Peritoneal Mesothelial Cells

2010 ◽  
Vol 17 (5) ◽  
pp. 757-763 ◽  
Author(s):  
Jun Wu ◽  
Xiao Yang ◽  
Yun-Fang Zhang ◽  
Ya-Ning Wang ◽  
Mei Liu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Mrna Expression ◽  
Real Time Pcr ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Solution Treated ◽  
Tnf Α ◽  
Human Peritoneal Mesothelial Cells ◽  
Molecular Patterns ◽  
Dialysis Fluids

ABSTRACT The objective of this study was to investigate the effects of glucose-based peritoneal dialysis (PD) fluids and icodextrin-based PD fluids on the expression of Toll-like receptor 2 (TLR2)/TLR4 and subsequent ligand-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling and tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) mRNA expression in human peritoneal mesothelial cells (HPMCs). A human peritoneal mesothelial cell line (HMrSV5) was stimulated with glucose-based and icodextrin-based peritoneal dialysis fluids. Cell viability was assessed using MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. TLR2/TLR4 expression was determined by real-time PCR, Western blotting, and an immunofluorescence assay. In addition, cells were pretreated with different PD solutions and then incubated with Pam3CSK4 or lipopolysaccharide (LPS), and the degrees of MAPK and NF-κB activation were reflected by detecting the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and p65, using a Western blot method. TNF-α and IL-1β mRNA expression was measured by real-time PCR. Glucose-based peritoneal dialysis fluids suppressed the expression of TLR2 and TLR4 proteins in HPMCs. Challenge of cells with either Pam3CSK4 or LPS resulted in impaired TNF-α and IL-1β production. Moreover, reduced TLR2 and TLR4 levels in glucose-based peritoneal dialysis solution-treated mesothelial cells were accompanied by reduced p42/44 (ERK1/2), JNK, p38 MAPK, and NF-κB p65 phosphorylation upon TLR ligand engagement. No significant changes in MAPK and NF-κB signaling and TNF-α and IL-1β mRNA expression were observed in icodextrin-based PD solution-treated mesothelial cells. Glucose-based PD solution, but not icodextrin-based PD solution, downregulates expression of TLR2/TLR4 by human peritoneal mesothelial cells and triggers hyporesponsiveness to pathogen-associated molecular patterns.

Peritoneal Dialysis Fluid Induces P38-Dependent Inflammation in Human Mesothelial Cells

2011 ◽  
Vol 31 (3) ◽  
pp. 332-339 ◽  
Author(s):  
Andrea Riesenhuber ◽  
Klaus Kratochwill ◽  
Thorsten O. Bender ◽  
Regina Vargha ◽  
David C. Kasper ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Stress Response ◽  
Stress Responses ◽  
Mesothelial Cells ◽  
Hsp70 Expression ◽  
Peritoneal Mesothelial Cells ◽  
P38 Inhibitor ◽  
Peritoneal Dialysis Fluid ◽  
Human Peritoneal Mesothelial Cells ◽  
Ldh Release

BackgroundNoninfectious upregulation of proinflammatory pathways in mesothelial cells may represent an integral part of their stress response upon exposure to peritoneal dialysis fluids (PDF).ObjectiveThe aim of this study was to evaluate the role of the stress-inducible mitogen-activated protein kinase (MAPK) p38 in regulation of inflammatory and stress responses in mesothelial cells following in vitro exposure to PDF.Materials and MethodsHuman peritoneal mesothelial cells were exposed to Dianeal PD4 or Physioneal (Baxter AG, Vienna, Austria) containing 1.36% glucose and then allowed to recover. Phosphorylation of p38, induction of heat shock protein-70 (HSP70), release of lactate dehydrogenase (LDH), secretion of interleukin (IL)-8, gene transcription, and mRNA stability were assessed with and without the MAPK p38 inhibitor SB203580.ResultsExposure to Dianeal resulted in phosphorylation of p38 within 30 minutes (309% of control, p < 0.05) and increased IL-8 release (370% of control, p < 0.05), HSP70 expression (151% of control, p < 0.05), and LDH release (180% of control, p < 0.05). Exposure to Physioneal resulted in attenuated changes in IL-8, HSP70, and LDH. Addition of the p38 inhibitor SB203580 to Dianeal resulted in dampened IL-8 release (-55%; p < 0.05) and basal HSP70 expression, and unchanged LDH release. Effects of p38 on IL-8 were at transcriptional, posttranscriptional, and translational levels.ConclusionThese data confirm concordant p38-dependent upregulation of IL-8 and HSP70 following exposure to bioincompatible PDF. The MAPK p38 pathway therefore links proinflammatory processes and the cellular stress response in human peritoneal mesothelial cells.

scholarly journals Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells

2001 ◽  
Vol 12 (11) ◽  
pp. 2434-2441 ◽  
Author(s):  
JANUSZ WITOWSKI ◽  
JUSTYNA WISNIEWSKA ◽  
KATARZYNA KORYBALSKA ◽  
THORSTEN O. BENDER ◽  
ANDRZEJ BREBOROWICZ ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
Human Peritoneal Mesothelial Cells ◽  
And Function ◽  
The Impact

Abstract. Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.

scholarly journals Effect of Glucose on Intercellular Junctions of Cultured Human Peritoneal Mesothelial Cells

2000 ◽  
Vol 11 (11) ◽  
pp. 1969-1979
Author(s):  
TAKAFUMI ITO ◽  
NORIAKI YORIOKA ◽  
MASAO YAMAMOTO ◽  
KATSUKO KATAOKA ◽  
MICHIO YAMAKIDO
Keyword(s):  
Peritoneal Dialysis ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Intercellular Junctions ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Peritoneal Dialysis Fluid ◽  
Human Peritoneal Mesothelial Cells

Abstract. During continuous ambulatory peritoneal dialysis, the peritoneum is directly and continuously exposed to unphysiologic peritoneal dialysis fluid; the resulting mesothelial damage has been suggested to cause loss of ultrafiltration and dialysis efficacy. The present study investigated the effect of a high glucose concentration on cultured human peritoneal mesothelial cells to clarify the cause of decreased dialysis efficacy during prolonged peritoneal dialysis. High glucose caused a concentration-dependent decrease in cell proliferation, damage to the intercellular junctions, and excess production of transforming growth factor-β (TGF-β). The levels of intercellular junctional proteins (ZO-1, E-cadherin, and β-catenin) were decreased, and immuno-staining by anti—ZO-1 and anti— β-catenin antibodies became weaker and often discontinuous along the cell contour. Mannitol had similar but weaker effects at the same osmolality, and an anti—TGF-β neutralizing antibody reduced the effects of high glucose. Therefore, these effects were induced not only by glucose itself but also by hyperosmolality and by a glucose-induced increase of TGF-β. These findings suggest that the peritoneal mesothelium is damaged by prolonged peritoneal dialysis using high glucose dialysate and that impairment of the intercellular junctions of peritoneal mesothelial cells by high glucose dialysate induces peritoneal hyperpermeability and a progressive reduction in dialysis efficacy.

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