作者
Laura Brandolini, Michele d’Angelo, Rubina Novelli, Vanessa Castelli, Cristina Giorgio, Anna Sirico, Pasquale Cocchiaro, Francesco D’Egidio, Elisabetta Benedetti, Claudia Cristiano, Antonella Bugatti, Anna Ruocco, Pier Giorgio Amendola, Carmine Talarico, Candida Manelfi, Daniela Iaconis, Andrea Beccari, Andreza U Quadros, Thiago M Cunha, Arnaldo Caruso, Roberto Russo, Annamaria Cimini, Andrea Aramini, Marcello Allegretti
发表日期
2022/5/25
期刊
Cell death & disease
卷号
13
期号
5
页码范围
500
出版商
Nature Publishing Group UK
简介
Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent and impairing side effects of the antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind and activate complement component 5a receptor 1 (C5aR1) and that this binding is crucial in the etiology of paclitaxel-induced CIPN and anaphylaxis. Starting from our previous data demonstrating the role of interleukin (IL)-8 in paclitaxel-induced neuronal toxicity, we searched for proteins that activate IL-8 expression and, by using the Exscalate platform for molecular docking simulations, we predicted the high affinity of C5aR1 with paclitaxel. By in vitro studies, we confirmed the specific and competitive nature of the C5aR1-paclitaxel binding and found that it triggers intracellularly the NFkB/P38 pathway and c-Fos. In F11 neuronal cells and rat dorsal root ganglia, C5aR1 inhibition …
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L Brandolini, M d'Angelo, R Novelli, V Castelli… - Cell death & disease, 2022