Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells

Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds wit...

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Main Authors: Aline Müller, Maria Lozoya, Xiaoying Chen, Volkmar Weissig, Mahtab Nourbakhsh
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/12/3322
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author Aline Müller
Maria Lozoya
Xiaoying Chen
Volkmar Weissig
Mahtab Nourbakhsh
author_facet Aline Müller
Maria Lozoya
Xiaoying Chen
Volkmar Weissig
Mahtab Nourbakhsh
author_sort Aline Müller
collection DOAJ
description Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential has attracted widespread attention in scientific research. This study aimed to study the potential anti-inflammatory effects of a natural oil compound, farnesol, in primary human renal proximal tubule epithelial cell (RPTEC) culture. Farnesol was encapsulated in lipid-based small unilamellar vesicles (SUVs) to overcome its insolubility in cell culture medium. The cell attachment of empty vesicles (SUVs) and farnesol-loaded vesicles (farnesol-SUVs) was examined using BODIPY, a fluorescent dye with hydrophobic properties. Next, we used multiple protein, RNA, and protein phosphorylation arrays to investigate the impact of farnesol on inflammatory signaling in RPTECs. The results indicated that farnesol inhibits TNF-α/IL-1β-induced phosphorylation of the PI3 kinase p85 subunit and subsequent transcriptional activation of the inflammatory genes TNFRSF9, CD27, TNFRSF8, DR6, FAS, IL-7, and CCL2. Therefore, farnesol may be a promising natural compound for treating CKD.
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spelling doaj.art-fe09ea8a366e435da9d484cbe883e61a2023-12-22T13:55:19ZengMDPI AGBiomedicines2227-90592023-12-011112332210.3390/biomedicines11123322Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial CellsAline Müller0Maria Lozoya1Xiaoying Chen2Volkmar Weissig3Mahtab Nourbakhsh4Department of Geriatric Medicine, RWTH Aachen University Hospital, 52074 Aachen, GermanyCollege of Pharmacy, Midwestern University, Glendale, AZ 85308, USADepartment of Geriatric Medicine, RWTH Aachen University Hospital, 52074 Aachen, GermanyCollege of Pharmacy, Midwestern University, Glendale, AZ 85308, USADepartment of Geriatric Medicine, RWTH Aachen University Hospital, 52074 Aachen, GermanyChronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential has attracted widespread attention in scientific research. This study aimed to study the potential anti-inflammatory effects of a natural oil compound, farnesol, in primary human renal proximal tubule epithelial cell (RPTEC) culture. Farnesol was encapsulated in lipid-based small unilamellar vesicles (SUVs) to overcome its insolubility in cell culture medium. The cell attachment of empty vesicles (SUVs) and farnesol-loaded vesicles (farnesol-SUVs) was examined using BODIPY, a fluorescent dye with hydrophobic properties. Next, we used multiple protein, RNA, and protein phosphorylation arrays to investigate the impact of farnesol on inflammatory signaling in RPTECs. The results indicated that farnesol inhibits TNF-α/IL-1β-induced phosphorylation of the PI3 kinase p85 subunit and subsequent transcriptional activation of the inflammatory genes TNFRSF9, CD27, TNFRSF8, DR6, FAS, IL-7, and CCL2. Therefore, farnesol may be a promising natural compound for treating CKD.https://www.mdpi.com/2227-9059/11/12/3322humanrenal proximal tubule epithelial cellsTNF-αIL-1βnanoliposomesfarnesol
spellingShingle Aline Müller
Maria Lozoya
Xiaoying Chen
Volkmar Weissig
Mahtab Nourbakhsh
Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
Biomedicines
human
renal proximal tubule epithelial cells
TNF-α
IL-1β
nanoliposomes
farnesol
title Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
title_full Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
title_fullStr Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
title_full_unstemmed Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
title_short Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
title_sort farnesol inhibits pi3 kinase signaling and inflammatory gene expression in primary human renal epithelial cells
topic human
renal proximal tubule epithelial cells
TNF-α
IL-1β
nanoliposomes
farnesol
url https://www.mdpi.com/2227-9059/11/12/3322
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AT xiaoyingchen farnesolinhibitspi3kinasesignalingandinflammatorygeneexpressioninprimaryhumanrenalepithelialcells
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