title: The uremic solute p-cresol decreases leukocyte transendothelial migration in vitro.
abstract: Chronic renal failure (CRF) patients display an immunodeficiency state, and uremic solutes that accumulate during CRF may be involved in this immunodeficiency. In this study, we examined whether the uremic solute para-cresol (p-cresol), at concentrations similar to those found in patients, alters leukocyte transmigration in vitro. We found that p-cresol significantly inhibited monocyte THP-1 cell line and PBMCs transmigration across IL-1beta-stimulated human umbilical vein endothelial cell (HUVEC) in a static two-compartment model. This inhibitory effect of p-cresol persisted in the presence of a physiologic concentration of human serum albumin. In order to investigate the mechanism involved, expression of endothelial chemokines, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and IL-8 and membrane expression of junctional adhesion molecule A (JAM-A or JAM-1) were studied. We found that p-cresol decreased mRNA expression of the chemokine fractalkine in IL-1beta-stimulated HUVEC, without modifying mRNA expression of MCP-1 and IL-8. In addition, p-cresol decreased IL-1beta-induced expression of membrane-bound and soluble forms of fractalkine and impaired the membrane expression of JAM-A. Taken together, these results suggest that p-cresol, by impairing leukocyte transendothelial migration, plays a role in the immune dysfunction of uremic patients.
authors.affiliation: UMR INSERM 608, Faculté de Pharmacie, UFR de Pharmacie, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13005 Marseille, France. valerie.faure@pharmacie.univ-mrs.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Faure
authors.forename: Claire
authors.initials: C
authors.lastname: Cerini
authors.forename: Pascale
authors.initials: P
authors.lastname: Paul
authors.forename: Yvon
authors.initials: Y
authors.lastname: Berland
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunet
mesh_terms: D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D003408:Cresols / Q000276:immunology / Q000494:pharmacology* / Q000652:urine; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000652:urine; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000652:urine; D007962:Leukocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D014511:Uremia / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000652:urine
chemical_list: D003408:Cresols; D016207:Cytokines; D012333:RNA, Messenger; C032538:4-cresol