Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23
Abstract Background Botulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment. Results In vivo, BTX-A attenuated chronic compression injury (CCI)-induced pain in rats, and reduced production of pro-inflammatory factors. The inhibition of BTX-A to ex...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-020-00501-4 |
| _version_ | 1818350712393826304 |
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| author | Xuan Wang Sheng Tian Hansen Wang Pan Liu Heqing Zheng Lanxiang Wu Qian Liu Wei Wu |
| author_facet | Xuan Wang Sheng Tian Hansen Wang Pan Liu Heqing Zheng Lanxiang Wu Qian Liu Wei Wu |
| author_sort | Xuan Wang |
| collection | DOAJ |
| description | Abstract Background Botulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment. Results In vivo, BTX-A attenuated chronic compression injury (CCI)-induced pain in rats, and reduced production of pro-inflammatory factors. The inhibition of BTX-A to expression and phosphorylation of SNAP23 were partly reversed by TLR2/MyD88 upregulation. In LPS-stimulated microglia, we also found that BTX-A suppressed TLR2, MyD88, p-SNAP23 and SNAP23 expression, and reduced pro-inflammatory factors secretion. Upregulation of TLR2 and MyD88 recued the inhibition of BTX-A to LPS-induced activation of SNAP23. Then, we demonstrated that BTX-A reduced expression of SNAP23 through inhibition of IKKα/β phosphorylation. Besides, the inhibition of BTX-A to LPS-induced upregulation of SNAP23 can be reversed by proteasome inhibitor. NEDD4, an E3 ubiquitin ligase, was proved to be bind with SNAP23. BTX-A reduced expression of SNAP23 via facilitating ubiquitin-mediated degradation of SNAP23. Conclusion Overall, our data demonstrated that BTX-A attenuated NP via reducing the secretion of pro-inflammatory factors from microglia by inhibition of TLR2/MyD88 signaling. BTX-A downregulated expression of SNAP23 via reducing phosphorylation of IKKα/β, and enhancing ubiquitination of SNAP23 by suppressing TLR2/MyD88 signaling. |
| first_indexed | 2024-12-13T18:26:12Z |
| format | Article |
| id | doaj.art-4372de6893f444e58d043bbe159199a3 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-13T18:26:12Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-4372de6893f444e58d043bbe159199a32022-12-21T23:35:36ZengBMCCell & Bioscience2045-37012020-12-0110111310.1186/s13578-020-00501-4Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23Xuan Wang0Sheng Tian1Hansen Wang2Pan Liu3Heqing Zheng4Lanxiang Wu5Qian Liu6Wei Wu7Department of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityImaging Department, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityAbstract Background Botulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment. Results In vivo, BTX-A attenuated chronic compression injury (CCI)-induced pain in rats, and reduced production of pro-inflammatory factors. The inhibition of BTX-A to expression and phosphorylation of SNAP23 were partly reversed by TLR2/MyD88 upregulation. In LPS-stimulated microglia, we also found that BTX-A suppressed TLR2, MyD88, p-SNAP23 and SNAP23 expression, and reduced pro-inflammatory factors secretion. Upregulation of TLR2 and MyD88 recued the inhibition of BTX-A to LPS-induced activation of SNAP23. Then, we demonstrated that BTX-A reduced expression of SNAP23 through inhibition of IKKα/β phosphorylation. Besides, the inhibition of BTX-A to LPS-induced upregulation of SNAP23 can be reversed by proteasome inhibitor. NEDD4, an E3 ubiquitin ligase, was proved to be bind with SNAP23. BTX-A reduced expression of SNAP23 via facilitating ubiquitin-mediated degradation of SNAP23. Conclusion Overall, our data demonstrated that BTX-A attenuated NP via reducing the secretion of pro-inflammatory factors from microglia by inhibition of TLR2/MyD88 signaling. BTX-A downregulated expression of SNAP23 via reducing phosphorylation of IKKα/β, and enhancing ubiquitination of SNAP23 by suppressing TLR2/MyD88 signaling.https://doi.org/10.1186/s13578-020-00501-4Neuropathic painBotulinum toxin type AMicrogliaSynaptosome associated protein 23 |
| spellingShingle | Xuan Wang Sheng Tian Hansen Wang Pan Liu Heqing Zheng Lanxiang Wu Qian Liu Wei Wu Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23 Cell & Bioscience Neuropathic pain Botulinum toxin type A Microglia Synaptosome associated protein 23 |
| title | Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23 |
| title_full | Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23 |
| title_fullStr | Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23 |
| title_full_unstemmed | Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23 |
| title_short | Botulinum toxin type A alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting TLR2/MyD88 and SNAP23 |
| title_sort | botulinum toxin type a alleviates neuropathic pain and suppresses inflammatory cytokines release from microglia by targeting tlr2 myd88 and snap23 |
| topic | Neuropathic pain Botulinum toxin type A Microglia Synaptosome associated protein 23 |
| url | https://doi.org/10.1186/s13578-020-00501-4 |
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