TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro

Frontiers in Pharmacology

Eunsoo Kim¹  Seung-Bin Park¹  Soeun Jeon²  Hae-kyu Kim²  Yesul Kim²  Hyeon-Jeong Lee²  Young-Hoon Jung²  Jae-young Kwon²  Heekee Kim³ 

[1] Department of Anesthesia and Pain Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea;Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, South Korea;Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, United States;

关键词: CIPN;    paclitaxel;    dorsal root ganglion;    50B11;    TNF-α;    TRPV1;   

DOI  :  10.3389/fphar.2022.842779

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown