P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines.

Abstract

BACKGROUND:

Infectious diseases are among the most morbid events in uremia. The uremic toxin p-cresol may play a role in the immunodeficiency of uremia by depressing phagocyte functional capacity. Leukocyte adhesion to endothelium, a key event in the immune response, is mediated by endothelial adhesion molecules. These include intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, which are induced by various inflammatory cytokines. We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion.

METHODS:

Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta). Thereafter, the endothelial molecules ICAM-1, VCAM-1, and E-selectin were quantitated and the monocyte (THP-1) adhesion to HUVEC measured.

RESULTS:

P-cresol decreased cytokine-induced protein and mRNA expression of ICAM-1 and VCAM-1. In addition, p-cresol significantly decreased the adhesion of THP-1 to cytokine-stimulated HUVEC.

CONCLUSIONS:

P-cresol may play a role in the immune defect of uremic patients by inhibiting cytokine-induced endothelial adhesion molecule expression and endothelium/monocyte adhesion.

• Authors: Laetitia Dou, Claire Cerini, Philippe Brunet, Catherine Guilianelli, Valérie Moal, Georges Grau, Rita De Smet, Raymond Vanholder, José Sampol, Yvon Berland
• Journal: Kidney international (Kidney Int) Vol. 62 Issue 6 Pg. 1999-2009 (Dec 2002) ISSN: 0085-2538 [Print] United States
• PMID: 12427124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cresols
• Interleukin-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• 4-cresol

Topics

• Antineoplastic Agents (pharmacology)
• Cell Adhesion (drug effects, immunology)
• Cells, Cultured
• Cresols (toxicity)
• Down-Regulation (drug effects)
• Endothelium, Vascular (cytology, drug effects, immunology)
• Humans
• Intercellular Adhesion Molecule-1 (genetics)
• Interleukin-1 (pharmacology)
• Leukocytes (cytology)
• RNA, Messenger (analysis)
• Tumor Necrosis Factor-alpha (pharmacology)
• Umbilical Veins (cytology)
• Uremia (immunology, pathology)
• Vascular Cell Adhesion Molecule-1 (genetics)