title: p-Cresyl sulfate suppresses lipopolysaccharide-induced anti-bacterial immune responses in murine macrophages in vitro.
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.
authors.affiliation: Yakult Central Institute, 5-11 Izumi, Kunitachi-Shi, Tokyo 186-8650, Japan. Electronic address: takahiro-shiba@yakult.co.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shiba
authors.affiliation: Yakult Central Institute, 5-11 Izumi, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Makino
authors.affiliation: Yakult Central Institute, 5-11 Izumi, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Yakult Central Institute, 5-11 Izumi, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kato
authors.affiliation: Yakult Central Institute, 5-11 Izumi, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Yakult Central Institute, 5-11 Izumi, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Kimiyuki
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism; D001119:Arginase / Q000378:metabolism; D001419:Bacteria / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D003408:Cresols / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D007111:Immunity, Cellular / Q000187:drug effects*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D000067996:RAW 264.7 Cells; D013463:Sulfuric Acid Esters / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000954:Antigens, Surface; D003408:Cresols; D016207:Cytokines; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D013463:Sulfuric Acid Esters; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; C408690:4-cresol sulfate; D001119:Arginase
keywords: Cytokine; Nitric oxide; Peritoneal macrophages; RAW264.7 cells; p-Cresyl sulphate