ApoA-I binding protein (AIBP) regulates transient receptor potential vanilloid 1 (TRPV1) activity in rat dorsal root ganglion neurons by selective disruption of toll-like receptor 4 (TLR4)-lipid rafts

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2024-10-14 DOI:10.1016/j.bbi.2024.10.017

Yan Li , Megan L. Uhelski , Robert Y. North , Luke B. Farson , Christopher B. Bankston , Gavin H. Roland , Dwight H. Fan , Katherine N. Sheffield , Amy Jia , Dana Orlando , Mario Heles , Tony L. Yaksh , Yury I. Miller , Therese A. Kosten , Patrick M. Dougherty

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引用次数: 0

Abstract

Toll-like receptor 4 (TLR4) and the transient receptor potential vanilloid subtype 1 (TRPV1) are both upregulated and play key roles in the induction and expression of paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Using Apolipoprotein A-I binding protein, non-specific cholesterol depletion, TLR4 mis-sense rats and a TLR4 inhibitor, we demonstrate that co-localization of TRPV1 with TLR4 to cholesterol-rich lipid membrane rafts in nociceptors is essential for its normal activation as well as for its exaggerated activation that underlies the development and expression of CIPN. The findings suggest that TLR4-lipid rafts may have an essential role in numerous neuroinflammatory and neuropathic pain conditions. This mechanism is also generalized to female rats for the first time.

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载脂蛋白A-I结合蛋白（AIBP）通过选择性破坏toll样受体4（TLR4）脂质筏来调节大鼠背根神经节神经元中瞬时受体电位香草素1（TRPV1）的活性。

在紫杉醇相关化疗诱导的周围神经病变（CIPN）的诱导和表达过程中，Toll 样受体 4（TLR4）和瞬时受体电位香草素亚型 1（TRPV1）均上调并发挥关键作用。通过使用载脂蛋白 A-I 结合蛋白、非特异性胆固醇耗竭、TLR4 错义大鼠和 TLR4 抑制剂，我们证明了 TRPV1 与 TLR4 共同定位到痛觉感受器中富含胆固醇的脂质膜筏对其正常激活以及导致 CIPN 发生和表达的过度激活至关重要。研究结果表明，TLR4-脂质膜筏可能在多种神经炎症和神经病理性疼痛病症中起着至关重要的作用。这一机制还首次被推广到雌性大鼠身上。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.