Paclitaxel treatment activates receptors for mitochondrial damage associated molecular patterns in the choroid plexus

ZAMANI, Alemeh, Lucie KUBÍČKOVÁ, Petr DUBOVÝ a Marek JOUKAL. Paclitaxel treatment activates receptors for mitochondrial damage associated molecular patterns in the choroid plexus. 2019.

Základní údaje

• Originální název: Paclitaxel treatment activates receptors for mitochondrial damage associated molecular patterns in the choroid plexus
• Autoři: ZAMANI, Alemeh, Lucie KUBÍČKOVÁ, Petr DUBOVÝ a Marek JOUKAL.
• Vydání: 2019.

Další údaje

• Typ výsledku: Konferenční abstrakt
• Utajení: není předmětem státního či obchodního tajemství
• Organizační jednotka: Lékařská fakulta

Anotace

Introduction: A major side effect of chemotherapeutic agent paclitaxel is peripheral neuropathy caused by mitochondrial degeneration in axons of peripheral nerves. We hypothesize that released damage-associated molecular patterns (DAMPs) from degenerated axons may affect the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus (CP) via toll-like receptor 9 (TLR9) and formyl peptide receptor 2 (FPR2). Therefore, we aimed to investigate the expression of TLR9 and FPR2 in the CP after paclitaxel treatment. Material and Methods: In our experiments, we intraperitoneally injected 4 doses (1, 3, 5, and 7 days; cumulative 8 mg/kg) of Paclitaxel or vehiculum (control) in Wistar rats. The animals were sacrificed 1, 7, 14 and 21 days after the last application together with naive rats. We analysed the expression level of TLR9 and FPR2 using immunohistochemical detection and quantification in choroid plexus. Results: We found TLR9 and FPR2 immunopositivity in the cytoplasm and the plasma membrane of CP epithelial cells. TLR9 and FPR2 expression level were significantly higher in the CP when examined one day after the last IP injection of paclitaxel, in comparison with controls and naive. Interestingly, the expression level further increased with the time, being highest at 21 days after the last paclitaxel injection. Conclusions: Our data show that paclitaxel application causes indirect molecular changes in the CP, based on the release of DAMPs. Up-regulation of TLR9 and FPR2 could potentially result in the release of pro-inflammatory cytokines and alter the structure of tight-junction proteins, which are essential for the functionality of the B-CSF barrier. Our data provides the possible molecular mechanism of the neuroinflammation in the CNS caused by paclitaxel.