P-Cresyl sulfate suppresses lipopolysaccharide-induced anti-bacterial immune responses in murine macrophages in vitro. (14th March 2016)

• Record Type: Journal Article
• Authors: Shiba, Takahiro; Makino, Ikuyo; Kawakami, Koji; Kato, Ikuo; Kobayashi, Toshihide; Kaneko, Kimiyuki
• Is Part Of: Toxicology letters. Volume 245(2016)
• Page Start: 24
• Page End: 30
• Publication Date: 2016-03-14
• Subjects: APC allophycocyanin -- CKD chronic kidney disease -- ELISA enzyme-linked immunosorbent assay -- FITC fluorescein isothiocyanate -- IFN interferon -- IL interleukin -- iNOS inducible nitric oxide synthase -- LPS lipopolysaccharide -- mAb monoclonal antibody -- MFI mean fluorescence intensity -- NK cells natural killer cells -- NO nitric oxide -- pCS p-cresyl sulfate -- PBS phosphate-buffered saline -- PI propidium iodide -- ROS reactive oxygen species; p-Cresyl sulphate -- RAW264.7 cells -- Peritoneal macrophages -- Cytokine -- Nitric oxide; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.01.009
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: p -Cresyl sulfate (pCS) decreased nitric oxide production in RAW264.7 cells. pCS suppressed IL-12 p40 and increased IL-10 production in RAW264.7 cells. pCS suppressed lipopolysaccharide-induced CD40 expression on RAW264.7 cells. pCS suppressed IL-12 p40 and p70 and increased IL-10 in peritoneal macrophages. Abstract: p -Cresyl sulfate (pCS) is a known uremic toxin that is metabolized from p -cresol produced by intestinal bacteria. Abnormal accumulation of pCS in the blood is a characteristic of chronic kidney disease (CKD). pCS is suggested to cause immune dysfunction and increase the risk of infectious diseases in CKD patients. In this study, we focused on the effects of pCS on macrophage functions related to host defense. We evaluated the effects of pCS on cytokine production, nitric oxide (NO) production, arginase activity, expression of cell-surface molecules, and phagocytosis in the macrophage-like cell line, RAW264.7. pCS significantly decreased interleukin (IL)-12 p40 production and increased IL-10 production. pCS also decreased NO production, but did not influence arginase activity. pCS suppressed lipopolysaccharide-induced CD40 expression on the cell surface, but did not influence phagocytosis. We further assessed whether the effects of pCS observed in the macrophage-like cell line were consistent in primary macrophages. Similar to RAW264.7 cells, pCS decreased IL-12 p40 and p70 production and increased IL-10 production in primary peritoneal macrophages. These data indicate that pCS suppresses certain macrophage functions that contribute to host defense, and may play a role in CKD-related immune dysfunction.