p-Cresyl sulfate decreases peripheral B cells in mice with adenine-induced renal dysfunction.
Toxicol Appl Pharmacol
; 342: 50-59, 2018 03 01.
Article
em En
| MEDLINE
| ID: mdl-29407365
Infection is a major cause of mortality in chronic kidney disease (CKD) patients. Although immune dysfunction is a risk factor for infection in CKD patients, its causes are not fully elucidated. In the present study, we evaluated whether p-cresyl sulfate (pCS), an intestinal bacteria-derived uremic toxin, was involved in immune dysfunction in CKD. We used osmotic pumps to establish adenine-induced renal dysfunction mice with a chronically high blood pCS concentration. Analysis of lymphocyte subsets revealed that pCS significantly reduced peripheral B cells in renal dysfunction mice. In vitro, pCS inhibited interleukin (IL)-7-induced proliferation of CD43+ B-cell progenitors and suppressed IL-7-induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) in these cells. Cell cycle analysis showed that pCS significantly decreased the percentage of CD43+ B-cell progenitors in S phase and increased that in G1 phase. These results suggest that pCS suppressed IL-7-induced STAT5 signaling and inhibited B-cell progenitor proliferation, leading to reduction of peripheral B cells in adenine-induced renal dysfunction mice. Therefore, pCS decreases peripheral B cells by inhibiting proliferation of CD43+ B-cell progenitors and is a likely cause of immune dysfunction in CKD patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Ésteres do Ácido Sulfúrico
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Linfócitos B
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Adenina
/
Cresóis
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Insuficiência Renal Crônica
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article