TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro
Background: Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts cancer survivors’ quality of life and is challenging to treat with existing drugs for neuropathic pain. TNF-α is known to potentiate TRPV1 activity, which contributes to CIPN. Here, we assessed the role of TMI-1, a TNF-...
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| Format: | Article |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.842779/full |
| _version_ | 1818683310298103808 |
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| author | Yesul Kim Young-Hoon Jung Seung-Bin Park Heekee Kim Jae-young Kwon Hae-kyu Kim Hyeon-Jeong Lee Soeun Jeon Eunsoo Kim Eunsoo Kim |
| author_facet | Yesul Kim Young-Hoon Jung Seung-Bin Park Heekee Kim Jae-young Kwon Hae-kyu Kim Hyeon-Jeong Lee Soeun Jeon Eunsoo Kim Eunsoo Kim |
| author_sort | Yesul Kim |
| collection | DOAJ |
| description | Background: Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts cancer survivors’ quality of life and is challenging to treat with existing drugs for neuropathic pain. TNF-α is known to potentiate TRPV1 activity, which contributes to CIPN. Here, we assessed the role of TMI-1, a TNF-α-converting enzyme inhibitor, in paclitaxel (PAC)-induced neurotoxicity in dorsal root ganglion (DRG) cells.Materials and Methods: Immortalized DRG neuronal 50B11 cells were cultured and treated with PAC or PAC with TMI-1 following neuronal differentiation. Cell viability, analysis of neurite growth, immunofluorescence, calcium flow cytometry, western blotting, quantitative RT-PCR, and cytokine quantitation by ELISA were performed to determine the role of TMI-1 in neurotoxicity in neuronal cells.Results: PAC administration decreased the length of neurites and upregulated the expression of TRPV1 in 50B11 cells. TMI-1 administration showed a protective effect by suppressing inflammatory signaling, and secretion of TNF-α.Conclusion: TMI-1 partially protects against paclitaxel-induced neurotoxicity by reversing the upregulation of TRPV1 and decreasing levels of inflammatory cytokines, including TNF-α, IL-1β, and IL-6 in neuronal cells. |
| first_indexed | 2024-12-17T10:32:42Z |
| format | Article |
| id | doaj.art-af6e7c2336ef4afd9bc054a0e3fce306 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T10:32:42Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-af6e7c2336ef4afd9bc054a0e3fce3062022-12-21T21:52:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.842779842779TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In VitroYesul Kim0Young-Hoon Jung1Seung-Bin Park2Heekee Kim3Jae-young Kwon4Hae-kyu Kim5Hyeon-Jeong Lee6Soeun Jeon7Eunsoo Kim8Eunsoo Kim9Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaDepartment of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, United StatesDepartment of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South KoreaDepartment of Anesthesia and Pain Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaBackground: Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts cancer survivors’ quality of life and is challenging to treat with existing drugs for neuropathic pain. TNF-α is known to potentiate TRPV1 activity, which contributes to CIPN. Here, we assessed the role of TMI-1, a TNF-α-converting enzyme inhibitor, in paclitaxel (PAC)-induced neurotoxicity in dorsal root ganglion (DRG) cells.Materials and Methods: Immortalized DRG neuronal 50B11 cells were cultured and treated with PAC or PAC with TMI-1 following neuronal differentiation. Cell viability, analysis of neurite growth, immunofluorescence, calcium flow cytometry, western blotting, quantitative RT-PCR, and cytokine quantitation by ELISA were performed to determine the role of TMI-1 in neurotoxicity in neuronal cells.Results: PAC administration decreased the length of neurites and upregulated the expression of TRPV1 in 50B11 cells. TMI-1 administration showed a protective effect by suppressing inflammatory signaling, and secretion of TNF-α.Conclusion: TMI-1 partially protects against paclitaxel-induced neurotoxicity by reversing the upregulation of TRPV1 and decreasing levels of inflammatory cytokines, including TNF-α, IL-1β, and IL-6 in neuronal cells.https://www.frontiersin.org/articles/10.3389/fphar.2022.842779/fullCIPNpaclitaxeldorsal root ganglion50B11TNF-αTRPV1 |
| spellingShingle | Yesul Kim Young-Hoon Jung Seung-Bin Park Heekee Kim Jae-young Kwon Hae-kyu Kim Hyeon-Jeong Lee Soeun Jeon Eunsoo Kim Eunsoo Kim TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro Frontiers in Pharmacology CIPN paclitaxel dorsal root ganglion 50B11 TNF-α TRPV1 |
| title | TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro |
| title_full | TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro |
| title_fullStr | TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro |
| title_full_unstemmed | TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro |
| title_short | TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro |
| title_sort | tmi 1 tnf α converting enzyme inhibitor protects against paclitaxel induced neurotoxicity in the drg neuronal cells in vitro |
| topic | CIPN paclitaxel dorsal root ganglion 50B11 TNF-α TRPV1 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.842779/full |
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