Impairment of MCP-1 expression in mesothelial cells exposed to peritoneal dialysis fluid by osmotic stress and acidic stress.
BACKGROUND
Bacterial 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.


METHODS
Human 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 chemoattractant protein-1 (MCP-1), nuclear factor-κB (NF-κB), mitogen-activated protein (MAP) kinases, and MAP kinase phosphatase-1 (MKP-1).


RESULTS
We 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.


CONCLUSIONS
These 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.
Ogata
Ryouji
R
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Hiramatsu
Nobuhiko
N
Hayakawa
Kunihiro
K
Nakajima
Shotaro
S
Yao
Jian
J
Kobayashi
Tetsuro
T
Kitamura
Masanori
M
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000187:drug effects*; D015314:Dialysis Solutions / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009995:Osmosis; D013312:Stress, Physiological
D018932:Chemokine CCL2; D015314:Dialysis Solutions