Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1
The relationship of uric acid with macrophages has not been fully elucidated. We investigated the effect of uric acid on the proinflammatory ability of human macrophages and then examined the possible molecular mechanism involved. Primary human monocytes were differentiated into macrophages for subs...
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doaj-4dfb4d9235a94e089f204faa09c169b12020-11-25T02:04:01ZengMDPI AGBiomolecules2218-273X2020-04-011057657610.3390/biom10040576Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1Camilo P. Martínez-Reyes0Aarón N. Manjarrez-Reyna1Lucia A. Méndez-García2José A. Aguayo-Guerrero3Beatriz Aguirre-Sierra4Rafael Villalobos-Molina5Yolanda López-Vidal6Karen Bobadilla7Galileo Escobedo8Laboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, 06726 Mexico City, MexicoLaboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, 06726 Mexico City, MexicoLaboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, 06726 Mexico City, MexicoLaboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, 06726 Mexico City, MexicoLaboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, 06726 Mexico City, MexicoUnidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, 54090 Mexico City, MexicoPrograma de Inmunología Molecular Microbiana, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 Mexico City, MexicoDepartment of Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, 14080 Mexico City, MexicoLaboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, 06726 Mexico City, MexicoThe relationship of uric acid with macrophages has not been fully elucidated. We investigated the effect of uric acid on the proinflammatory ability of human macrophages and then examined the possible molecular mechanism involved. Primary human monocytes were differentiated into macrophages for subsequent exposure to 0, 0.23, 0.45, or 0.9 mmol/L uric acid for 12 h, in the presence or absence of 1 mmol/L probenecid. Flow cytometry was used to measure proinflammatory marker production and phagocytic activity that was quantified as a percentage of GFP-labeled <i>Escherichia coli</i> positive macrophages. qPCR was used to measure the macrophage expression of the urate anion transporter 1 (URAT1). As compared to control cells, the production of tumor necrosis factor-alpha (TNF-alpha), toll-like receptor 4 (TLR4), and cluster of differentiation (CD) 11c was significantly increased by uric acid. In contrast, macrophages expressing CD206, CX3C-motif chemokine receptor 1 (CX3CR1), and C-C chemokine receptor type 2 (CCR2) were significantly reduced. Uric acid progressively increased macrophage phagocytic activity and downregulated URAT1 expression. Probenecid—a non-specific blocker of URAT1-dependent uric acid transport—inhibited both proinflammatory cytokine production and phagocytic activity in macrophages that were exposed to uric acid. These results suggest that uric acid has direct proinflammatory effects on macrophages possibly via URAT1.https://www.mdpi.com/2218-273X/10/4/576macrophageuric acidTNF-alphaTLR4phagocytosisprobenecid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Camilo P. Martínez-Reyes Aarón N. Manjarrez-Reyna Lucia A. Méndez-García José A. Aguayo-Guerrero Beatriz Aguirre-Sierra Rafael Villalobos-Molina Yolanda López-Vidal Karen Bobadilla Galileo Escobedo |
spellingShingle |
Camilo P. Martínez-Reyes Aarón N. Manjarrez-Reyna Lucia A. Méndez-García José A. Aguayo-Guerrero Beatriz Aguirre-Sierra Rafael Villalobos-Molina Yolanda López-Vidal Karen Bobadilla Galileo Escobedo Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1 Biomolecules macrophage uric acid TNF-alpha TLR4 phagocytosis probenecid |
author_facet |
Camilo P. Martínez-Reyes Aarón N. Manjarrez-Reyna Lucia A. Méndez-García José A. Aguayo-Guerrero Beatriz Aguirre-Sierra Rafael Villalobos-Molina Yolanda López-Vidal Karen Bobadilla Galileo Escobedo |
author_sort |
Camilo P. Martínez-Reyes |
title |
Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1 |
title_short |
Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1 |
title_full |
Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1 |
title_fullStr |
Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1 |
title_full_unstemmed |
Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1 |
title_sort |
uric acid has direct proinflammatory effects on human macrophages by increasing proinflammatory mediators and bacterial phagocytosis probably via urat1 |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2020-04-01 |
description |
The relationship of uric acid with macrophages has not been fully elucidated. We investigated the effect of uric acid on the proinflammatory ability of human macrophages and then examined the possible molecular mechanism involved. Primary human monocytes were differentiated into macrophages for subsequent exposure to 0, 0.23, 0.45, or 0.9 mmol/L uric acid for 12 h, in the presence or absence of 1 mmol/L probenecid. Flow cytometry was used to measure proinflammatory marker production and phagocytic activity that was quantified as a percentage of GFP-labeled <i>Escherichia coli</i> positive macrophages. qPCR was used to measure the macrophage expression of the urate anion transporter 1 (URAT1). As compared to control cells, the production of tumor necrosis factor-alpha (TNF-alpha), toll-like receptor 4 (TLR4), and cluster of differentiation (CD) 11c was significantly increased by uric acid. In contrast, macrophages expressing CD206, CX3C-motif chemokine receptor 1 (CX3CR1), and C-C chemokine receptor type 2 (CCR2) were significantly reduced. Uric acid progressively increased macrophage phagocytic activity and downregulated URAT1 expression. Probenecid—a non-specific blocker of URAT1-dependent uric acid transport—inhibited both proinflammatory cytokine production and phagocytic activity in macrophages that were exposed to uric acid. These results suggest that uric acid has direct proinflammatory effects on macrophages possibly via URAT1. |
topic |
macrophage uric acid TNF-alpha TLR4 phagocytosis probenecid |
url |
https://www.mdpi.com/2218-273X/10/4/576 |
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