Bortezomib (BTZ) is used as a chemotherapeutic agent for the treatment of multiple myeloma. Nevertheless, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. Thus, in this study we examined signaling pathways of interleukin-6 (IL-6) and transient receptor potential ankyrin 1 (TRPA1) in the sensory nerves responsible for neuropathic pain induced by BTZ and further determined if influencing the pathways can improve neuropathic pain. ELISA and western blot analysis were used to examine the levels of IL-6, and IL-6 receptor (IL-6R), TRPA1 and p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical and cold sensitivity in a rat model. Our results showed that systemic injection of BTZ increased mechanical pain and cold sensitivity as compared with control animals. Data also showed that protein expression of TRPA1 and IL-6R was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical and cold sensitivity in control rats and BTZ rats. Notably, the inhibitory effect of blocking TRPA1 was smaller in BTZ rats than that in control rats. In addition, a blockade of IL-6 signal attenuated intracellular p38-MAPK and JNK in the sensory neuron. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. In conclusion, we revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ, including IL-6-TRPA1, suggesting that blocking these signals is beneficial to alleviate neuropathic pain during BTZ intervention.

• MeSH
• acetanilidy farmakologie   MeSH
• analgetika farmakologie   MeSH
• bortezomib * MeSH
• chinoxaliny farmakologie   MeSH
• fosforylace MeSH
• inhibitory proteasomu * MeSH
• interleukin-6 antagonisté a inhibitory   metabolismus   MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• kationtový kanál TRPA1 antagonisté a inhibitory   metabolismus   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nervové receptory metabolismus   účinky léků   MeSH
• neuralgie chemicky indukované   farmakoterapie   metabolismus   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• práh bolesti účinky léků   MeSH
• puriny farmakologie   MeSH
• pyraziny farmakologie   MeSH
• receptory interleukinu-6 antagonisté a inhibitory   metabolismus   účinky léků   MeSH
• signální transdukce MeSH
• spinální ganglia metabolismus   patofyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Heterogenous expression of recombinant proteins in milk of livestock at a large scale is very labour-intensive to be achieved with current transgenic animals, and usually seen as time-consuming, expensive and technically most challenging. Here we describe a convenient system for transient production of recombinant human growth hormone and its extensive use in recombinant protein production for therapeutic purposes. In this study, an adenoviral vector containing the GFP gene and hGH gene was constructed for direct infusion into the epithelium of mammary glands of goats via the teat canal during the period of natural lactation. Western-blot analysis of milk samples obtained from all of the viral-treated founders indicated that the recombinant hGH (rhGH) was secreted into the milk of the goats. The concentrations of rhGH in milk ranged from 0.6 to 2.4 mg/ml and lasted for more than 10 days during lactation. These data suggest that it is possible to produce larger amounts of recombinant human growth hormone in the milk of livestock animals by using replication-defective adenoviruses.

• MeSH
• Adenoviridae genetika   MeSH
• financování organizované MeSH
• genetické vektory genetika   MeSH
• geneticky modifikovaná zvířata MeSH
• kozy genetika   metabolismus   MeSH
• lidé MeSH
• mléko metabolismus   MeSH
• modely genetické MeSH
• růstový hormon genetika   metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH