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Toxicol Lett ; 263: 1-5, 2016 Nov 30.
Article in English | MEDLINE | ID: mdl-27760375

ABSTRACT

Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×106 cells/mL) were incubated with pCS (10, 25, or 50µg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12.1%, 39.8±7.75%, 43.7±11.9%, respectively) compared to untreated cells (4.35±3.34%) after 6h incubation but only the lowest concentration increased this production after 12h (82.9±8.6%, 61±7.2%, 40.8±11.7%). Combined with LPS, the same results were observed. Regarding to phagocytosis, all concentrations were able to induce bead engulfment (35.4±2.71%, 30±3.04%, 23.28±4.58%). In addition, pCS (50µg/mL) was able to increase HLA-ABC and CD80 expression, showed a slight effect on HLA-DR expression and, no difference in basal CD86 levels. pCS can induce an increased oxidative burst and phagocytosis by human macrophages while no modulation of HLA-DR or CD86 expression was induced. Together, these results suggest that pCS induces macrophage activation but interfere in antigen processing, leading to a failure in adaptive immune response in CKD.


Subject(s)
Antigen Presentation/drug effects , Cresols/toxicity , Macrophages/drug effects , Monocytes/drug effects , Phagocytosis/drug effects , Respiratory Burst/drug effects , Sulfuric Acid Esters/toxicity , Antioxidants/metabolism , B7-1 Antigen/biosynthesis , HLA Antigens/biosynthesis , Humans , Lipopolysaccharides/pharmacology , Macrophages/immunology , Monocytes/immunology , Nitric Oxide/metabolism , U937 Cells , Uremia/metabolism
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