IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury

Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Qingyu Sun [verfasserIn] Tingting Hu [verfasserIn] Yurui Zhang [verfasserIn] Xiaotong Wang [verfasserIn] Jing Liu [verfasserIn] Wen Chen [verfasserIn] Chao Wei [verfasserIn] Dianxin Liu [verfasserIn] Weihua Wu [verfasserIn] Ting Lan [verfasserIn] Yumeng Ding [verfasserIn] Zhaoli Luo [verfasserIn] Meng Liu [verfasserIn] Danmin Shen [verfasserIn] Zhongnan Xiao [verfasserIn] Liye Hu [verfasserIn] Miaoyi Pang [verfasserIn] Yiran Ma [verfasserIn] Lei Shi [verfasserIn] Peipei Wang [verfasserIn] Jiannan Zhang [verfasserIn] Qian Li [verfasserIn] Fei Yang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2022.1012442

Katalog-ID:	DOAJ021368015

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520			\|a Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate.
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allfields	10.3389/fimmu.2022.1012442 doi (DE-627)DOAJ021368015 (DE-599)DOAJccf5dcf85e9944e394efa73ccfabf8f0 DE-627 ger DE-627 rakwb eng RC581-607 Qingyu Sun verfasserin aut IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate. itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1 Immunologic diseases. Allergy Qingyu Sun verfasserin aut Tingting Hu verfasserin aut Yurui Zhang verfasserin aut Xiaotong Wang verfasserin aut Jing Liu verfasserin aut Wen Chen verfasserin aut Chao Wei verfasserin aut Dianxin Liu verfasserin aut Weihua Wu verfasserin aut Ting Lan verfasserin aut Yumeng Ding verfasserin aut Zhaoli Luo verfasserin aut Meng Liu verfasserin aut Danmin Shen verfasserin aut Zhongnan Xiao verfasserin aut Liye Hu verfasserin aut Miaoyi Pang verfasserin aut Yiran Ma verfasserin aut Lei Shi verfasserin aut Peipei Wang verfasserin aut Jiannan Zhang verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Fei Yang verfasserin aut Fei Yang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1012442 kostenfrei https://doaj.org/article/ccf5dcf85e9944e394efa73ccfabf8f0 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012442/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
spelling	10.3389/fimmu.2022.1012442 doi (DE-627)DOAJ021368015 (DE-599)DOAJccf5dcf85e9944e394efa73ccfabf8f0 DE-627 ger DE-627 rakwb eng RC581-607 Qingyu Sun verfasserin aut IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate. itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1 Immunologic diseases. Allergy Qingyu Sun verfasserin aut Tingting Hu verfasserin aut Yurui Zhang verfasserin aut Xiaotong Wang verfasserin aut Jing Liu verfasserin aut Wen Chen verfasserin aut Chao Wei verfasserin aut Dianxin Liu verfasserin aut Weihua Wu verfasserin aut Ting Lan verfasserin aut Yumeng Ding verfasserin aut Zhaoli Luo verfasserin aut Meng Liu verfasserin aut Danmin Shen verfasserin aut Zhongnan Xiao verfasserin aut Liye Hu verfasserin aut Miaoyi Pang verfasserin aut Yiran Ma verfasserin aut Lei Shi verfasserin aut Peipei Wang verfasserin aut Jiannan Zhang verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Fei Yang verfasserin aut Fei Yang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1012442 kostenfrei https://doaj.org/article/ccf5dcf85e9944e394efa73ccfabf8f0 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012442/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfields_unstemmed	10.3389/fimmu.2022.1012442 doi (DE-627)DOAJ021368015 (DE-599)DOAJccf5dcf85e9944e394efa73ccfabf8f0 DE-627 ger DE-627 rakwb eng RC581-607 Qingyu Sun verfasserin aut IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate. itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1 Immunologic diseases. Allergy Qingyu Sun verfasserin aut Tingting Hu verfasserin aut Yurui Zhang verfasserin aut Xiaotong Wang verfasserin aut Jing Liu verfasserin aut Wen Chen verfasserin aut Chao Wei verfasserin aut Dianxin Liu verfasserin aut Weihua Wu verfasserin aut Ting Lan verfasserin aut Yumeng Ding verfasserin aut Zhaoli Luo verfasserin aut Meng Liu verfasserin aut Danmin Shen verfasserin aut Zhongnan Xiao verfasserin aut Liye Hu verfasserin aut Miaoyi Pang verfasserin aut Yiran Ma verfasserin aut Lei Shi verfasserin aut Peipei Wang verfasserin aut Jiannan Zhang verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Fei Yang verfasserin aut Fei Yang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1012442 kostenfrei https://doaj.org/article/ccf5dcf85e9944e394efa73ccfabf8f0 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012442/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsGer	10.3389/fimmu.2022.1012442 doi (DE-627)DOAJ021368015 (DE-599)DOAJccf5dcf85e9944e394efa73ccfabf8f0 DE-627 ger DE-627 rakwb eng RC581-607 Qingyu Sun verfasserin aut IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate. itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1 Immunologic diseases. Allergy Qingyu Sun verfasserin aut Tingting Hu verfasserin aut Yurui Zhang verfasserin aut Xiaotong Wang verfasserin aut Jing Liu verfasserin aut Wen Chen verfasserin aut Chao Wei verfasserin aut Dianxin Liu verfasserin aut Weihua Wu verfasserin aut Ting Lan verfasserin aut Yumeng Ding verfasserin aut Zhaoli Luo verfasserin aut Meng Liu verfasserin aut Danmin Shen verfasserin aut Zhongnan Xiao verfasserin aut Liye Hu verfasserin aut Miaoyi Pang verfasserin aut Yiran Ma verfasserin aut Lei Shi verfasserin aut Peipei Wang verfasserin aut Jiannan Zhang verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Fei Yang verfasserin aut Fei Yang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1012442 kostenfrei https://doaj.org/article/ccf5dcf85e9944e394efa73ccfabf8f0 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012442/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsSound	10.3389/fimmu.2022.1012442 doi (DE-627)DOAJ021368015 (DE-599)DOAJccf5dcf85e9944e394efa73ccfabf8f0 DE-627 ger DE-627 rakwb eng RC581-607 Qingyu Sun verfasserin aut IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate. itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1 Immunologic diseases. Allergy Qingyu Sun verfasserin aut Tingting Hu verfasserin aut Yurui Zhang verfasserin aut Xiaotong Wang verfasserin aut Jing Liu verfasserin aut Wen Chen verfasserin aut Chao Wei verfasserin aut Dianxin Liu verfasserin aut Weihua Wu verfasserin aut Ting Lan verfasserin aut Yumeng Ding verfasserin aut Zhaoli Luo verfasserin aut Meng Liu verfasserin aut Danmin Shen verfasserin aut Zhongnan Xiao verfasserin aut Liye Hu verfasserin aut Miaoyi Pang verfasserin aut Yiran Ma verfasserin aut Lei Shi verfasserin aut Peipei Wang verfasserin aut Jiannan Zhang verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Qian Li verfasserin aut Fei Yang verfasserin aut Fei Yang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1012442 kostenfrei https://doaj.org/article/ccf5dcf85e9944e394efa73ccfabf8f0 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012442/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
language	English
source	In Frontiers in Immunology 13(2022) volume:13 year:2022
sourceStr	In Frontiers in Immunology 13(2022) volume:13 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1 Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Qingyu Sun @@aut@@ Tingting Hu @@aut@@ Yurui Zhang @@aut@@ Xiaotong Wang @@aut@@ Jing Liu @@aut@@ Wen Chen @@aut@@ Chao Wei @@aut@@ Dianxin Liu @@aut@@ Weihua Wu @@aut@@ Ting Lan @@aut@@ Yumeng Ding @@aut@@ Zhaoli Luo @@aut@@ Meng Liu @@aut@@ Danmin Shen @@aut@@ Zhongnan Xiao @@aut@@ Liye Hu @@aut@@ Miaoyi Pang @@aut@@ Yiran Ma @@aut@@ Lei Shi @@aut@@ Peipei Wang @@aut@@ Jiannan Zhang @@aut@@ Qian Li @@aut@@ Fei Yang @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ021368015
language_de	englisch
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callnumber-first	R - Medicine
author	Qingyu Sun
spellingShingle	Qingyu Sun misc RC581-607 misc itaconate misc interleukin-10 misc neuropathic pain misc tricarboxylic acid cycle misc IRG1 misc Immunologic diseases. Allergy IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
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topic_title	RC581-607 IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury itaconate interleukin-10 neuropathic pain tricarboxylic acid cycle IRG1
topic	misc RC581-607 misc itaconate misc interleukin-10 misc neuropathic pain misc tricarboxylic acid cycle misc IRG1 misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc itaconate misc interleukin-10 misc neuropathic pain misc tricarboxylic acid cycle misc IRG1 misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc itaconate misc interleukin-10 misc neuropathic pain misc tricarboxylic acid cycle misc IRG1 misc Immunologic diseases. Allergy
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title	IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
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title_full	IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
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author_browse	Qingyu Sun Tingting Hu Yurui Zhang Xiaotong Wang Jing Liu Wen Chen Chao Wei Dianxin Liu Weihua Wu Ting Lan Yumeng Ding Zhaoli Luo Meng Liu Danmin Shen Zhongnan Xiao Liye Hu Miaoyi Pang Yiran Ma Lei Shi Peipei Wang Jiannan Zhang Qian Li Fei Yang
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title_sort	irg1/itaconate increases il-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
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title_auth	IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
abstract	Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate.
abstractGer	Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate.
abstract_unstemmed	Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate.
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title_short	IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
url	https://doi.org/10.3389/fimmu.2022.1012442 https://doaj.org/article/ccf5dcf85e9944e394efa73ccfabf8f0 https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012442/full https://doaj.org/toc/1664-3224
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The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. 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IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury

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