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Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice

Microglia, the resident macrophages, act as the first and main form of active immune defense in the central nervous system. Arginase 2 (Arg2) is an enzyme involved in L-arginine metabolism and is expressed in macrophages and nervous tissue. In this study, we determined whether the absence of Arg2 pl...

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Autores principales: Yin, Yuhua, Phạm, Thuỳ Linh, Shin, Juhee, Shin, Nara, Kang, Dong-Wook, Lee, Sun Yeul, Lee, Wonhyung, Kim, Cuk-Seong, Kim, Sang Ryong, Hong, Jinpyo, Kim, Dong-Woon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073606/
https://www.ncbi.nlm.nih.gov/pubmed/31979015
http://dx.doi.org/10.3390/jcm9020305
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author Yin, Yuhua
Phạm, Thuỳ Linh
Shin, Juhee
Shin, Nara
Kang, Dong-Wook
Lee, Sun Yeul
Lee, Wonhyung
Kim, Cuk-Seong
Kim, Sang Ryong
Hong, Jinpyo
Kim, Dong-Woon
author_facet Yin, Yuhua
Phạm, Thuỳ Linh
Shin, Juhee
Shin, Nara
Kang, Dong-Wook
Lee, Sun Yeul
Lee, Wonhyung
Kim, Cuk-Seong
Kim, Sang Ryong
Hong, Jinpyo
Kim, Dong-Woon
author_sort Yin, Yuhua
collection PubMed
description Microglia, the resident macrophages, act as the first and main form of active immune defense in the central nervous system. Arginase 2 (Arg2) is an enzyme involved in L-arginine metabolism and is expressed in macrophages and nervous tissue. In this study, we determined whether the absence of Arg2 plays a beneficial or detrimental role in the neuroinflammatory process. We then investigated whether the loss of Arg2 potentiated microglia activation and pain behaviors following nerve injury-induced neuropathic pain. A spinal nerve transection (SNT) experimental model was used to induce neuropathic pain in mice. As a result of the peripheral nerve injury, SNT induced microgliosis and astrogliosis in the spinal cord, and upregulated inflammatory signals in both wild-type (WT) and Arg2 knockout (KO) mice. Notably, inflammation increased significantly in the Arg2 KO group compared to the WT group. We also observed a more robust microgliosis and a lower mechanical threshold in the Arg2 KO group than those in the WT group. Furthermore, our data revealed a stronger upregulation of M1 pro-inflammatory cytokines, such as interleukin (IL)-1β, and a stronger downregulation of M2 anti-inflammatory cytokines, including IL4 and IL-10, in Arg2 KO mice. Additionally, stronger formation of enzyme-inducible nitric oxide synthase, oxidative stress, and decreased expression of CD206 were detected in the Arg2 KO group compared to the WT group. These results suggest that Arg2 deficiency contributes to inflammatory response. The reduction or the loss of Arg2 results in the stronger neuroinflammation in the spinal dorsal horn, followed by more severe pain behaviors arising from nerve injury-induced neuropathic pain.
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spelling pubmed-70736062020-03-20 Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice Yin, Yuhua Phạm, Thuỳ Linh Shin, Juhee Shin, Nara Kang, Dong-Wook Lee, Sun Yeul Lee, Wonhyung Kim, Cuk-Seong Kim, Sang Ryong Hong, Jinpyo Kim, Dong-Woon J Clin Med Article Microglia, the resident macrophages, act as the first and main form of active immune defense in the central nervous system. Arginase 2 (Arg2) is an enzyme involved in L-arginine metabolism and is expressed in macrophages and nervous tissue. In this study, we determined whether the absence of Arg2 plays a beneficial or detrimental role in the neuroinflammatory process. We then investigated whether the loss of Arg2 potentiated microglia activation and pain behaviors following nerve injury-induced neuropathic pain. A spinal nerve transection (SNT) experimental model was used to induce neuropathic pain in mice. As a result of the peripheral nerve injury, SNT induced microgliosis and astrogliosis in the spinal cord, and upregulated inflammatory signals in both wild-type (WT) and Arg2 knockout (KO) mice. Notably, inflammation increased significantly in the Arg2 KO group compared to the WT group. We also observed a more robust microgliosis and a lower mechanical threshold in the Arg2 KO group than those in the WT group. Furthermore, our data revealed a stronger upregulation of M1 pro-inflammatory cytokines, such as interleukin (IL)-1β, and a stronger downregulation of M2 anti-inflammatory cytokines, including IL4 and IL-10, in Arg2 KO mice. Additionally, stronger formation of enzyme-inducible nitric oxide synthase, oxidative stress, and decreased expression of CD206 were detected in the Arg2 KO group compared to the WT group. These results suggest that Arg2 deficiency contributes to inflammatory response. The reduction or the loss of Arg2 results in the stronger neuroinflammation in the spinal dorsal horn, followed by more severe pain behaviors arising from nerve injury-induced neuropathic pain. MDPI 2020-01-22 /pmc/articles/PMC7073606/ /pubmed/31979015 http://dx.doi.org/10.3390/jcm9020305 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yin, Yuhua
Phạm, Thuỳ Linh
Shin, Juhee
Shin, Nara
Kang, Dong-Wook
Lee, Sun Yeul
Lee, Wonhyung
Kim, Cuk-Seong
Kim, Sang Ryong
Hong, Jinpyo
Kim, Dong-Woon
Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
title Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
title_full Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
title_fullStr Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
title_full_unstemmed Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
title_short Arginase 2 Deficiency Promotes Neuroinflammation and Pain Behaviors Following Nerve Injury in Mice
title_sort arginase 2 deficiency promotes neuroinflammation and pain behaviors following nerve injury in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073606/
https://www.ncbi.nlm.nih.gov/pubmed/31979015
http://dx.doi.org/10.3390/jcm9020305
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