Peritoneal dialysis fluids can alter HSP expression in human peritoneal mesothelial cells.
BACKGROUND
Acute exposure of mesothelial cells to peritoneal dialysis fluid (PDF) has been shown not only to result in injury but also to induce cytoprotective heat shock proteins (HSP). The aim of the present study was to evaluate the expression of HSP in a more chronic in vitro PDF exposure system, searching for a role of glucose degradation products (GDP).


METHODS
Human peritoneal mesothelial cells (HPMC) were chronically incubated in filter- or heat-sterilized PDF (mixed 1:1 with cell culture medium), or in control cell culture medium. After incubation periods of 1, 3 and 10 days, cell extract was assessed for Ezrin, Hsp27 and Hsp72, and supernatant for IL-6 and IL-8. After 24-h exposure to the GDP 3.4-di-deoxyglucosone-3-ene (3.4-DGE), HPMC were assessed for expression of Hsp27 and Hsp72, and for release of LDH, IL-6 and IL-8.


RESULTS
In vitro PDF exposure for more than 1 day resulted in reduced cell mass, lower expression of the epithelial marker Ezrin and depressed cellular levels of both HSP, associated with increased IL-6 and IL-8 release. These effects occurred earlier and stronger with heat-sterilized than with filter-sterilized PDF. Exposure of HPMC to 3.4-DGE resulted in suppression of HSP, and increased release of LDH, IL-6 and IL-8.


CONCLUSIONS
Our data show that GDP (dys)regulate the mesothelial cell stress response. This was associated with reduced cell mass, loss of the epithelial phenotype and sterile cellular inflammation following extended exposure to heat-sterilized PDF. Toxic effects of PDF might thus be extended to reduced mesothelial cell stress responses.
Bender
Thorsten O
TO
Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Böhm
Michael
M
Kratochwill
Klaus
K
Vargha
Regina
R
Riesenhuber
Andrea
A
Witowski
Janusz
J
Jörres
Achim
A
Wieslander
Anders
A
Aufricht
Christoph
C
D001202:Ascitic Fluid / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015314:Dialysis Solutions / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D010530:Peritoneal Dialysis; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D015314:Dialysis Solutions; D005947:Glucose; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D000099149:Ezrin