Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages.
OBJECTIVE:The uremic toxin Indoxyl-3-sulphate (IS), a ligand of Aryl hydrocarbon Receptor (AhR), raises in blood during early renal dysfunction as a consequence of tubular damage, which may be present even when eGFR is normal or only moderately reduced, and promotes cardiovascular damage and monocyt...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4771744?pdf=render |
| _version_ | 1811205442584444928 |
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| author | Chiara Barisione Silvano Garibaldi Anna Lisa Furfaro Mariapaola Nitti Daniela Palmieri Mario Passalacqua Anna Garuti Daniela Verzola Alessia Parodi Pietro Ameri Paola Altieri Patrizia Fabbi Pier Francesco Ferrar Claudio Brunelli Violeta Arsenescu Manrico Balbi Domenico Palombo Giorgio Ghigliotti |
| author_facet | Chiara Barisione Silvano Garibaldi Anna Lisa Furfaro Mariapaola Nitti Daniela Palmieri Mario Passalacqua Anna Garuti Daniela Verzola Alessia Parodi Pietro Ameri Paola Altieri Patrizia Fabbi Pier Francesco Ferrar Claudio Brunelli Violeta Arsenescu Manrico Balbi Domenico Palombo Giorgio Ghigliotti |
| author_sort | Chiara Barisione |
| collection | DOAJ |
| description | OBJECTIVE:The uremic toxin Indoxyl-3-sulphate (IS), a ligand of Aryl hydrocarbon Receptor (AhR), raises in blood during early renal dysfunction as a consequence of tubular damage, which may be present even when eGFR is normal or only moderately reduced, and promotes cardiovascular damage and monocyte-macrophage activation. We previously found that patients with abdominal aortic aneurysms (AAAs) have higher CD14+CD16+ monocyte frequency and prevalence of moderate chronic kidney disease (CKD) than age-matched control subjects. Here we aimed to evaluate the IS levels in plasma from AAA patients and to investigate in vitro the effects of IS concentrations corresponding to mild-to-moderate CKD on monocyte polarization and macrophage differentiation. METHODS:Free IS plasma levels, monocyte subsets and laboratory parameters were evaluated on blood from AAA patients and eGFR-matched controls. THP-1 monocytes, treated with IS 1, 10, 20 μM were evaluated for CD163 expression, AhR signaling and then induced to differentiate into macrophages by PMA. Their phenotype was evaluated both at the stage of semi-differentiated and fully differentiated macrophages. AAA and control sera were similarly used to treat THP-1 monocytes and the resulting macrophage phenotype was analyzed. RESULTS:IS plasma concentration correlated positively with CD14+CD16+ monocytes and was increased in AAA patients. In THP-1 cells, IS promoted CD163 expression and transition to macrophages with hallmarks of classical (IL-6, CCL2, COX2) and alternative phenotype (IL-10, PPARγ, TGF-β, TIMP-1), via AhR/Nrf2 activation. Analogously, AAA sera induced differentiation of macrophages with enhanced IL-6, MCP1, TGF-β, PPARγ and TIMP-1 expression. CONCLUSION:IS skews monocyte differentiation toward low-inflammatory, profibrotic macrophages and may contribute to sustain chronic inflammation and maladaptive vascular remodeling. |
| first_indexed | 2024-04-12T03:31:39Z |
| format | Article |
| id | doaj.art-df9b062c73184a7380123cf8e5afe9e1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:31:39Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-df9b062c73184a7380123cf8e5afe9e12022-12-22T03:49:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014927610.1371/journal.pone.0149276Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages.Chiara BarisioneSilvano GaribaldiAnna Lisa FurfaroMariapaola NittiDaniela PalmieriMario PassalacquaAnna GarutiDaniela VerzolaAlessia ParodiPietro AmeriPaola AltieriPatrizia FabbiPier Francesco FerrarClaudio BrunelliVioleta ArsenescuManrico BalbiDomenico PalomboGiorgio GhigliottiOBJECTIVE:The uremic toxin Indoxyl-3-sulphate (IS), a ligand of Aryl hydrocarbon Receptor (AhR), raises in blood during early renal dysfunction as a consequence of tubular damage, which may be present even when eGFR is normal or only moderately reduced, and promotes cardiovascular damage and monocyte-macrophage activation. We previously found that patients with abdominal aortic aneurysms (AAAs) have higher CD14+CD16+ monocyte frequency and prevalence of moderate chronic kidney disease (CKD) than age-matched control subjects. Here we aimed to evaluate the IS levels in plasma from AAA patients and to investigate in vitro the effects of IS concentrations corresponding to mild-to-moderate CKD on monocyte polarization and macrophage differentiation. METHODS:Free IS plasma levels, monocyte subsets and laboratory parameters were evaluated on blood from AAA patients and eGFR-matched controls. THP-1 monocytes, treated with IS 1, 10, 20 μM were evaluated for CD163 expression, AhR signaling and then induced to differentiate into macrophages by PMA. Their phenotype was evaluated both at the stage of semi-differentiated and fully differentiated macrophages. AAA and control sera were similarly used to treat THP-1 monocytes and the resulting macrophage phenotype was analyzed. RESULTS:IS plasma concentration correlated positively with CD14+CD16+ monocytes and was increased in AAA patients. In THP-1 cells, IS promoted CD163 expression and transition to macrophages with hallmarks of classical (IL-6, CCL2, COX2) and alternative phenotype (IL-10, PPARγ, TGF-β, TIMP-1), via AhR/Nrf2 activation. Analogously, AAA sera induced differentiation of macrophages with enhanced IL-6, MCP1, TGF-β, PPARγ and TIMP-1 expression. CONCLUSION:IS skews monocyte differentiation toward low-inflammatory, profibrotic macrophages and may contribute to sustain chronic inflammation and maladaptive vascular remodeling.http://europepmc.org/articles/PMC4771744?pdf=render |
| spellingShingle | Chiara Barisione Silvano Garibaldi Anna Lisa Furfaro Mariapaola Nitti Daniela Palmieri Mario Passalacqua Anna Garuti Daniela Verzola Alessia Parodi Pietro Ameri Paola Altieri Patrizia Fabbi Pier Francesco Ferrar Claudio Brunelli Violeta Arsenescu Manrico Balbi Domenico Palombo Giorgio Ghigliotti Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages. PLoS ONE |
| title | Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages. |
| title_full | Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages. |
| title_fullStr | Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages. |
| title_full_unstemmed | Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages. |
| title_short | Moderate Increase of Indoxyl Sulfate Promotes Monocyte Transition into Profibrotic Macrophages. |
| title_sort | moderate increase of indoxyl sulfate promotes monocyte transition into profibrotic macrophages |
| url | http://europepmc.org/articles/PMC4771744?pdf=render |
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