Show simple item record

dc.creatorBrandolini, Laura
dc.creatorD'Angelo, Michele
dc.creatorNovelli, Rubina
dc.creatorCastelli, Vanessa
dc.creatorGiorgio, Cristina
dc.creatorSirico, Anna
dc.creatorCocchiaro, Pasquale
dc.creatorD'Egidio, Francesco
dc.creatorBenedetti, Elisabetta
dc.creatorCristiano, Claudia
dc.creatorBugatti, Antonella
dc.creatorRuocco, Anna
dc.creatorAmendola, Pier Giorgio
dc.creatorTalarico, Carmine
dc.creatorManelfi, Candida
dc.creatorIaconis, Daniela
dc.creatorBeccari, Andrea
dc.creatorQuadros, Andreza U.
dc.creatorCunha, Thiago M.
dc.creatorCaruso, Arnaldo
dc.creatorRusso, Roberto
dc.creatorCimini, Annamaria
dc.creatorAramini, Andrea
dc.creatorAllegratti, Marcello
dc.identifier.citationBrandolini, L., d’Angelo, M., Novelli, R. et al. Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions. Cell Death Dis 13, 500 (2022).
dc.description.abstractChemotherapy-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 protected from paclitaxel-induced neuropathological effects, while in paclitaxel-treated mice, the absence (knock-out mice) or the inhibition of C5aR1 significantly ameliorated CIPN symptoms—in terms of cold and mechanical allodynia—and reduced the chronic pathological state in the paw. Finally, we found that C5aR1 inhibition can counteract paclitaxel-induced anaphylactic cytokine release in macrophages in vitro, as well as the onset of HSRs in mice. Altogether these data identified C5aR1 as a key mediator and a new potential pharmacological target for the prevention and treatment of CIPN and HSRs induced by paclitaxel.
dc.format.extent15 pages
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartCell Death & Disease, Vol. 13
dc.relation.isreferencedbySpringer Nature
dc.rightsAttribution CC BY
dc.titlePaclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions
dc.type.genreJournal article
dc.contributor.groupCenter for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University)
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.temple.creatorCimini, Annamaria

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution CC BY
Except where otherwise noted, this item's license is described as Attribution CC BY