Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent
Recent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritonea...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2184 |
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| author | Olalla Ramil-Gómez Mirian López-Pardo Jennifer Adriana Fernández-Rodríguez Ana Rodríguez-Carmona Teresa Pérez-López Carlos Vaamonde-García Miguel Pérez-Fontán María José López-Armada |
| author_facet | Olalla Ramil-Gómez Mirian López-Pardo Jennifer Adriana Fernández-Rodríguez Ana Rodríguez-Carmona Teresa Pérez-López Carlos Vaamonde-García Miguel Pérez-Fontán María José López-Armada |
| author_sort | Olalla Ramil-Gómez |
| collection | DOAJ |
| description | Recent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritoneal membrane damage. Our ex vivo studies showed that IL-1β causes a drop in the mitochondrial membrane potential in cells from peritoneal effluent. Moreover, when mitochondrial damage was induced by inhibitors of mitochondrial function, a low-grade inflammatory response was generated. Interestingly, mitochondrial damage sensitized mesothelial cells, causing a significant increase in the inflammatory response induced by cytokines, in which ROS generation and NF-κB activation appear to be involved, since inflammation was counteracted by both mitoTEMPO (mitochondrial ROS scavenger) and BAY-117085 (NF-κB inhibitor). Furthermore, the natural anti-inflammatory antioxidant resveratrol significantly attenuated the inflammatory response, by reversing the decline in mitochondrial membrane potential and decreasing the expression of IL-8, COX-2 and PGE<sub>2</sub> caused by IL-1β. These findings suggest that IL-1β regulates mitochondrial function in mesothelial cells and that mitochondrial dysfunction could induce an inflammatory scenario that sensitizes these cells, causing significant amplification of the inflammatory response induced by cytokines. Resveratrol may represent a promising strategy in controlling the mesothelial inflammatory response to PD. |
| first_indexed | 2024-03-09T19:19:14Z |
| format | Article |
| id | doaj.art-93d45b838a334414a3ee2241da13ae5a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:19:14Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-93d45b838a334414a3ee2241da13ae5a2023-11-24T03:30:37ZengMDPI AGAntioxidants2076-39212022-11-011111218410.3390/antiox11112184Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis EffluentOlalla Ramil-Gómez0Mirian López-Pardo1Jennifer Adriana Fernández-Rodríguez2Ana Rodríguez-Carmona3Teresa Pérez-López4Carlos Vaamonde-García5Miguel Pérez-Fontán6María José López-Armada7Aging and Inflammation Research Laboratory, Institute for Biomedical Research of A Coruña (INIBIC), 15006 A Coruña, SpainAging and Inflammation Research Laboratory, Institute for Biomedical Research of A Coruña (INIBIC), 15006 A Coruña, SpainAging and Inflammation Research Laboratory, Institute for Biomedical Research of A Coruña (INIBIC), 15006 A Coruña, SpainAging and Inflammation Research Laboratory, Institute for Biomedical Research of A Coruña (INIBIC), 15006 A Coruña, SpainDivision of Nephrology, University Hospital A Coruña (CHUAC), 15006 A Coruña, SpainRheumatology Research Group, INIBIC, CHUAC, 15006 A Coruña, SpainEndocrine, Nutritional and Metabolic Diseases Group, Faculty of Health Sciences, A Coruña, INIBIC, 15006 A Coruña, SpainAging and Inflammation Research Laboratory, Institute for Biomedical Research of A Coruña (INIBIC), 15006 A Coruña, SpainRecent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritoneal membrane damage. Our ex vivo studies showed that IL-1β causes a drop in the mitochondrial membrane potential in cells from peritoneal effluent. Moreover, when mitochondrial damage was induced by inhibitors of mitochondrial function, a low-grade inflammatory response was generated. Interestingly, mitochondrial damage sensitized mesothelial cells, causing a significant increase in the inflammatory response induced by cytokines, in which ROS generation and NF-κB activation appear to be involved, since inflammation was counteracted by both mitoTEMPO (mitochondrial ROS scavenger) and BAY-117085 (NF-κB inhibitor). Furthermore, the natural anti-inflammatory antioxidant resveratrol significantly attenuated the inflammatory response, by reversing the decline in mitochondrial membrane potential and decreasing the expression of IL-8, COX-2 and PGE<sub>2</sub> caused by IL-1β. These findings suggest that IL-1β regulates mitochondrial function in mesothelial cells and that mitochondrial dysfunction could induce an inflammatory scenario that sensitizes these cells, causing significant amplification of the inflammatory response induced by cytokines. Resveratrol may represent a promising strategy in controlling the mesothelial inflammatory response to PD.https://www.mdpi.com/2076-3921/11/11/2184peritoneal dialysismitochondriaoxidative stressinflammationmesothelial cellsresveratrol |
| spellingShingle | Olalla Ramil-Gómez Mirian López-Pardo Jennifer Adriana Fernández-Rodríguez Ana Rodríguez-Carmona Teresa Pérez-López Carlos Vaamonde-García Miguel Pérez-Fontán María José López-Armada Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent Antioxidants peritoneal dialysis mitochondria oxidative stress inflammation mesothelial cells resveratrol |
| title | Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent |
| title_full | Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent |
| title_fullStr | Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent |
| title_full_unstemmed | Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent |
| title_short | Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent |
| title_sort | involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells from peritoneal dialysis effluent |
| topic | peritoneal dialysis mitochondria oxidative stress inflammation mesothelial cells resveratrol |
| url | https://www.mdpi.com/2076-3921/11/11/2184 |
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