Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain an...Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.展开更多
A previous study by our research group showed that nerve growth factor is involved in the onset of asthma through regulating SH2-Bβ expression in the lung and visceral primary afferent neurons of asthmatic mice. This...A previous study by our research group showed that nerve growth factor is involved in the onset of asthma through regulating SH2-Bβ expression in the lung and visceral primary afferent neurons of asthmatic mice. This study sought to assess the expression level of interleukin-1β in primary afferent neurons in C7-T5 spinal ganglia, spinal cord and lung in asthmatic mice after blockage of SH2-Bβ. The levels of interleukin-1β protein in primary afferent neurons in the C7-T5 spinal ganglia and lung were decreased, and interleukin-1β mRNA expression also down-regulated in the spinal cord, medulla oblongata and lung tissue after blockage of SH2-Bβ. Our findings indicate that SH2-Bβ can upregulate the expression of interleukin-1β in C7-T5 spinal ganglia, spinal cord and lung of asthmatic mice.展开更多
基金supported by National Institutes of Health Grants R01NS89479,R01NS045594 and ROINS055860
文摘Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.
基金grant from the Liaoning Provincial Education Bureau, No. 20060890
文摘A previous study by our research group showed that nerve growth factor is involved in the onset of asthma through regulating SH2-Bβ expression in the lung and visceral primary afferent neurons of asthmatic mice. This study sought to assess the expression level of interleukin-1β in primary afferent neurons in C7-T5 spinal ganglia, spinal cord and lung in asthmatic mice after blockage of SH2-Bβ. The levels of interleukin-1β protein in primary afferent neurons in the C7-T5 spinal ganglia and lung were decreased, and interleukin-1β mRNA expression also down-regulated in the spinal cord, medulla oblongata and lung tissue after blockage of SH2-Bβ. Our findings indicate that SH2-Bβ can upregulate the expression of interleukin-1β in C7-T5 spinal ganglia, spinal cord and lung of asthmatic mice.
