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Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment

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ZAMANI Alemeh KUBÍČKOVÁ Lucie HAŠANOVÁ Klaudia DUBOVÝ Petr JOUKAL Marek

Rok publikování 2021
Druh Konferenční abstrakty
Citace
Popis Introduction: Paclitaxel, a chemotherapeutic agent, causes toxic effects on peripheral nerves, often leading to neuropathic pain, yet with no treatment. Research shows that upregulated proinflammatory cytokines are involved in the development of neuropathic pain. However, the underlying mechanism of the spread of subsequent inflammation into the CNS remains to be explained. We aimed to study whether paclitaxel treatment has any direct or/and indirect effects on the choroid plexus (CP), one of the oldest and most understudied structures of the CNS. Methods: We examined whether the released damage-associated molecular patterns (DAPMs) can trigger key mediators of the immune system in the CP. To this end, we employed an in-vivo model of paclitaxel-induced neuropathic pain. Brains of Wistar rats treated with paclitaxel or its vehicle were harvested in different time points and were further analyzed using immunohistochemistry and western blot techniques. Moreover, to study the direct effect, Z310 cells an in-vitro model of CP were incubated with paclitaxel or different DAMPs for immunostaining and western blot analysis. Results: We found a higher expression of TLR9, TLR4, and FPR2 in CP epithelial cells when compared with controls in both in-vivo and in-vitro models. Next, we observed the production of proinflammatory cytokines, namely TNF?, IL6, and IL1ß, in CP and overexpression of regulatory proteins NF?B and STAT3. Conclusions: Our data show that paclitaxel application causes both indirect and direct molecular changes in the CP. Upregulation of immune mediators results in the release of proinflammatory cytokines and could potentially alter the structure and function of CP. Our data provides the possible molecular mechanism of the neuroinflammation in the CNS caused by paclitaxel.

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