Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells
Infected or damaged tissues release multiple “alert” molecules such as alarmins and damage-associated molecular patterns (DAMPs) that are recognized by innate immune receptors, and induce tissue inflammation, regeneration, and repair. Recently, an extract from inflamed rabbit skin inoculated with va...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6456 |
| _version_ | 1797554626325643264 |
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| author | Yu Fukuda Kazuki Nakajima Tatsuro Mutoh |
| author_facet | Yu Fukuda Kazuki Nakajima Tatsuro Mutoh |
| author_sort | Yu Fukuda |
| collection | DOAJ |
| description | Infected or damaged tissues release multiple “alert” molecules such as alarmins and damage-associated molecular patterns (DAMPs) that are recognized by innate immune receptors, and induce tissue inflammation, regeneration, and repair. Recently, an extract from inflamed rabbit skin inoculated with vaccinia virus (Neurotropin<sup>®</sup>, NTP) was found to induce infarct tolerance in mice receiving permanent ischemic attack to the middle cerebral artery. Likewise, we report herein that NTP prevented the neurite retraction in PC12 cells by nerve growth factor (NGF) deprivation. This effect was accompanied by interaction of Fyn with high-affinity NGF receptor TrkA. Sucrose density gradient subcellular fractionation of NTP-treated cells showed heretofore unidentified membrane fractions with a high-buoyant density containing Trk, B subunit of cholera toxin-bound ganglioside, flotillin-1 and Fyn. Additionally, these new membrane fractions also contained Toll-like receptor 4 (TLR4). Inhibition of TLR4 function by TAK-242 prevented the formation of these unidentified membrane fractions and suppressed neuroprotection by NTP. These observations indicate that NTP controls TrkA-mediated signaling through the formation of clusters of new membrane microdomains, thus providing a platform for crosstalk between neurotrophic and innate immune receptors. Neuroprotective mechanisms through the interaction with innate immune systems may provide novel mechanism for neuroprotection. |
| first_indexed | 2024-03-10T16:34:45Z |
| format | Article |
| id | doaj.art-49073bc980624e92bd61eadf4605f6b7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:34:45Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-49073bc980624e92bd61eadf4605f6b72023-11-20T12:33:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118645610.3390/ijms21186456Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 CellsYu Fukuda0Kazuki Nakajima1Tatsuro Mutoh2Department of Neurology and Neuroscience, Fujita Health University Hospital, Toyoake, Aichi 470-1192, JapanCenter for joint research facilities support, Research Promotion and Support Headquarters, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, JapanDepartment of Neurology and Neuroscience, Fujita Health University Hospital, Toyoake, Aichi 470-1192, JapanInfected or damaged tissues release multiple “alert” molecules such as alarmins and damage-associated molecular patterns (DAMPs) that are recognized by innate immune receptors, and induce tissue inflammation, regeneration, and repair. Recently, an extract from inflamed rabbit skin inoculated with vaccinia virus (Neurotropin<sup>®</sup>, NTP) was found to induce infarct tolerance in mice receiving permanent ischemic attack to the middle cerebral artery. Likewise, we report herein that NTP prevented the neurite retraction in PC12 cells by nerve growth factor (NGF) deprivation. This effect was accompanied by interaction of Fyn with high-affinity NGF receptor TrkA. Sucrose density gradient subcellular fractionation of NTP-treated cells showed heretofore unidentified membrane fractions with a high-buoyant density containing Trk, B subunit of cholera toxin-bound ganglioside, flotillin-1 and Fyn. Additionally, these new membrane fractions also contained Toll-like receptor 4 (TLR4). Inhibition of TLR4 function by TAK-242 prevented the formation of these unidentified membrane fractions and suppressed neuroprotection by NTP. These observations indicate that NTP controls TrkA-mediated signaling through the formation of clusters of new membrane microdomains, thus providing a platform for crosstalk between neurotrophic and innate immune receptors. Neuroprotective mechanisms through the interaction with innate immune systems may provide novel mechanism for neuroprotection.https://www.mdpi.com/1422-0067/21/18/6456Neurotropinlipid raftsGM1 ganglioside (GM1)TrkA tyrosine kinaseToll-like receptor4 (TLR4)Fyn |
| spellingShingle | Yu Fukuda Kazuki Nakajima Tatsuro Mutoh Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells International Journal of Molecular Sciences Neurotropin lipid rafts GM1 ganglioside (GM1) TrkA tyrosine kinase Toll-like receptor4 (TLR4) Fyn |
| title | Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells |
| title_full | Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells |
| title_fullStr | Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells |
| title_full_unstemmed | Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells |
| title_short | Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells |
| title_sort | neuroprotection by neurotropin through crosstalk of neurotrophic and innate immune receptors in pc12 cells |
| topic | Neurotropin lipid rafts GM1 ganglioside (GM1) TrkA tyrosine kinase Toll-like receptor4 (TLR4) Fyn |
| url | https://www.mdpi.com/1422-0067/21/18/6456 |
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