PMID- 20448242 OWN - NLM STAT- MEDLINE DCOM- 20111230 LR - 20200109 IS - 1718-4304 (Electronic) IS - 0896-8608 (Linking) VI - 31 IP - 1 DP - 2011 Jan-Feb TI - Impairment of MCP-1 expression in mesothelial cells exposed to peritoneal dialysis fluid by osmotic stress and acidic stress. PG - 80-9 LID - 10.3747/pdi.2009.00159 [doi] AB - 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-kappaB (NF-kappaB), 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-kappaB 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. CONCLUSION: 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-kappaB 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. FAU - Ogata, Ryouji AU - Ogata R AD - Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan. FAU - Hiramatsu, Nobuhiko AU - Hiramatsu N FAU - Hayakawa, Kunihiro AU - Hayakawa K FAU - Nakajima, Shotaro AU - Nakajima S FAU - Yao, Jian AU - Yao J FAU - Kobayashi, Tetsuro AU - Kobayashi T FAU - Kitamura, Masanori AU - Kitamura M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100506 PL - United States TA - Perit Dial Int JT - Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis JID - 8904033 RN - 0 (Chemokine CCL2) RN - 0 (Dialysis Solutions) SB - IM MH - Animals MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/*drug effects MH - Dialysis Solutions/*pharmacology MH - Epithelial Cells/*drug effects MH - Humans MH - Hydrogen-Ion Concentration MH - Mice MH - Monocytes/drug effects/physiology MH - Osmosis MH - Stress, Physiological EDAT- 2010/05/08 06:00 MHDA- 2011/12/31 06:00 CRDT- 2010/05/08 06:00 PHST- 2010/05/08 06:00 [entrez] PHST- 2010/05/08 06:00 [pubmed] PHST- 2011/12/31 06:00 [medline] AID - pdi.2009.00159 [pii] AID - 10.3747/pdi.2009.00159 [doi] PST - ppublish SO - Perit Dial Int. 2011 Jan-Feb;31(1):80-9. doi: 10.3747/pdi.2009.00159. Epub 2010 May 6.