Molecular and Cellular Respons of Choroid plexus to Paclitaxel
Treatment

a 2021

Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment

ZAMANI, Alemeh, Lucie KUBÍČKOVÁ, Klaudia HAŠANOVÁ, Petr DUBOVÝ, Marek JOUKAL et. al.

Základní údaje

Originální název

Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment

Autoři

ZAMANI, Alemeh, Lucie KUBÍČKOVÁ, Klaudia HAŠANOVÁ, Petr DUBOVÝ a Marek JOUKAL

Vydání

2021

Další údaje

Typ výsledku

Konferenční abstrakt

Utajení

není předmětem státního či obchodního tajemství

Změněno: 16. 2. 2023 17:39, Alemeh Zamani, Ph.D.

Anotace

V originále

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 TNFα, IL6, and IL1ß, in CP and overexpression of regulatory proteins NFκB 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.

Citovat

ZAMANI, Alemeh, Lucie KUBÍČKOVÁ, Klaudia HAŠANOVÁ, Petr DUBOVÝ a Marek JOUKAL. Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment. 2021.

@proceedings{2256978,
   author = {Zamani, Alemeh and Kubíčková, Lucie and Hašanová, Klaudia and Dubový, Petr and Joukal, Marek},
   title = {Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment},
   year = {2021}
}

TY  - CONF
ID  - 2256978
AU  - Zamani, Alemeh - Kubíčková, Lucie - Hašanová, Klaudia - Dubový, Petr - Joukal, Marek
PY  - 2021
TI  - Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment
N2  - 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 TNFα, IL6, and IL1ß, in CP and overexpression of regulatory proteins NFκB 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.
ER  -

ZAMANI, Alemeh, Lucie KUBÍČKOVÁ, Klaudia HAŠANOVÁ, Petr DUBOVÝ a Marek JOUKAL. \textit{Molecular and Cellular Respons of Choroid plexus to Paclitaxel Treatment}. 2021.

Podrobný výpis o publikaci