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Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain
Resident macrophages from dorsal root ganglia are important for the development of traumatic-induced neuropathic pain. In the first 5–7 days after a traumatic sciatic nerve injury (i.e., spinal nerve ligation (SNL), spared nerve injury (SNI), sciatic nerve transection or sciatic nerve ligation and t...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648812/ https://www.ncbi.nlm.nih.gov/pubmed/37958812 http://dx.doi.org/10.3390/ijms242115831 |
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author | Gheorghe, Roxana-Olimpia Grosu, Andreea Violeta Magercu, Melania Ghenghea, Mihail-Sebastian Zbarcea, Cristina Elena Tanase, Alexandra Negres, Simona Filippi, Alexandru Chiritoiu, Gabriela Gherghiceanu, Mihaela Dinescu, Sorina Gaina, Gisela Sapunar, Damir Ristoiu, Violeta |
author_facet | Gheorghe, Roxana-Olimpia Grosu, Andreea Violeta Magercu, Melania Ghenghea, Mihail-Sebastian Zbarcea, Cristina Elena Tanase, Alexandra Negres, Simona Filippi, Alexandru Chiritoiu, Gabriela Gherghiceanu, Mihaela Dinescu, Sorina Gaina, Gisela Sapunar, Damir Ristoiu, Violeta |
author_sort | Gheorghe, Roxana-Olimpia |
collection | PubMed |
description | Resident macrophages from dorsal root ganglia are important for the development of traumatic-induced neuropathic pain. In the first 5–7 days after a traumatic sciatic nerve injury (i.e., spinal nerve ligation (SNL), spared nerve injury (SNI), sciatic nerve transection or sciatic nerve ligation and transection), Ionized binding adapter protein 1 (Iba1) (+) resident macrophages cluster around dorsal root ganglia neurons, possibly contributing to nerve injury-induced hypersensitivity. Since infiltrating macrophages gradually recruited to the lesion site peak at about 7 days, the first few days post-lesion offer a window of opportunity when the contribution of Iba1 (+) resident macrophages to neuropathic pain pathogenesis could be investigated. Iba1 is an actin cross-linking cytoskeleton protein, specifically located only in macrophages and microglia. In this study, we explored the contribution of rat Iba1 (+) macrophages in SNL-induced neuropathic pain by using intra-ganglionic injections of naked Iba1-siRNA, delivered at the time the lesion occurred. The results show that 5 days after Iba1 silencing, Iba1 (+) resident macrophages are switched from an M1 (pro-inflammatory) phenotype to an M2 (anti-inflammatory) phenotype, which was confirmed by a significant decrease of M1 markers (CD32 and CD86), a significant increase of M2 markers (CD163 and Arginase-1), a reduced secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) and an increased release of pro-regenerative factors (BDNF, NGF and NT-3) which initiated the regrowth of adult DRG neurites and reduced SNL-induced neuropathic pain. Our data show for the first time, that it is possible to induce macrophages towards an anti-inflammatory phenotype by interacting with their cytoskeleton. |
format | Online Article Text |
id | pubmed-10648812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106488122023-10-31 Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain Gheorghe, Roxana-Olimpia Grosu, Andreea Violeta Magercu, Melania Ghenghea, Mihail-Sebastian Zbarcea, Cristina Elena Tanase, Alexandra Negres, Simona Filippi, Alexandru Chiritoiu, Gabriela Gherghiceanu, Mihaela Dinescu, Sorina Gaina, Gisela Sapunar, Damir Ristoiu, Violeta Int J Mol Sci Article Resident macrophages from dorsal root ganglia are important for the development of traumatic-induced neuropathic pain. In the first 5–7 days after a traumatic sciatic nerve injury (i.e., spinal nerve ligation (SNL), spared nerve injury (SNI), sciatic nerve transection or sciatic nerve ligation and transection), Ionized binding adapter protein 1 (Iba1) (+) resident macrophages cluster around dorsal root ganglia neurons, possibly contributing to nerve injury-induced hypersensitivity. Since infiltrating macrophages gradually recruited to the lesion site peak at about 7 days, the first few days post-lesion offer a window of opportunity when the contribution of Iba1 (+) resident macrophages to neuropathic pain pathogenesis could be investigated. Iba1 is an actin cross-linking cytoskeleton protein, specifically located only in macrophages and microglia. In this study, we explored the contribution of rat Iba1 (+) macrophages in SNL-induced neuropathic pain by using intra-ganglionic injections of naked Iba1-siRNA, delivered at the time the lesion occurred. The results show that 5 days after Iba1 silencing, Iba1 (+) resident macrophages are switched from an M1 (pro-inflammatory) phenotype to an M2 (anti-inflammatory) phenotype, which was confirmed by a significant decrease of M1 markers (CD32 and CD86), a significant increase of M2 markers (CD163 and Arginase-1), a reduced secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) and an increased release of pro-regenerative factors (BDNF, NGF and NT-3) which initiated the regrowth of adult DRG neurites and reduced SNL-induced neuropathic pain. Our data show for the first time, that it is possible to induce macrophages towards an anti-inflammatory phenotype by interacting with their cytoskeleton. MDPI 2023-10-31 /pmc/articles/PMC10648812/ /pubmed/37958812 http://dx.doi.org/10.3390/ijms242115831 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gheorghe, Roxana-Olimpia Grosu, Andreea Violeta Magercu, Melania Ghenghea, Mihail-Sebastian Zbarcea, Cristina Elena Tanase, Alexandra Negres, Simona Filippi, Alexandru Chiritoiu, Gabriela Gherghiceanu, Mihaela Dinescu, Sorina Gaina, Gisela Sapunar, Damir Ristoiu, Violeta Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain |
title | Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain |
title_full | Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain |
title_fullStr | Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain |
title_full_unstemmed | Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain |
title_short | Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain |
title_sort | switching rat resident macrophages from m1 to m2 phenotype by iba1 silencing has analgesic effects in snl-induced neuropathic pain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648812/ https://www.ncbi.nlm.nih.gov/pubmed/37958812 http://dx.doi.org/10.3390/ijms242115831 |
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