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Red nucleus interleukin-1β evokes tactile allodynia through activation of JAK/STAT3 and JNK signaling pathways.
J Neurosci Res. 2018 12; 96(12):1847-1861.JN

Abstract

We previously reported that interleukin-1β (IL-1β) in the red nucleus (RN) is involved in pain modulation and exerts a facilitatory effect in the development of neuropathic pain. Here, we explored the actions of signaling pathways, including the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-κB (NF-κB) pathways, on RN IL-1β-mediated pain modulation. After a single dose of recombinant rat IL-1β (rrIL-1β, 10 ng) injected into the RN in normal rats, a tactile allodynia was evoked in the contralateral but not ipsilateral hindpaw, commencing 75 min and peaking 120 min postinjection. Up-regulated protein levels of phospho-STAT3 (p-STAT3) and p-JNK were observed in the RN 120 min after rrIL-1β injection, the increases of p-STAT3 and p-JNK were blocked by anti-IL-1β antibody. However, the expression levels of p-ERK, p-p38 MAPK, and NF-κB in the RN were not affected by rrIL-1β injection. RN neurons and astrocytes contributed to IL-1β-evoked up-regulation of p-STAT3 and p-JNK. Further studies demonstrated that injection of the JAK2 antagonist AG490 or JNK antagonist SP600125 into the RN 30 min prior to the administration of rrIL-1β could completely prevent IL-1β-evoked tactile allodynia, while injection of the ERK antagonist PD98059, p38 MAPK antagonist SB203580, or NF-κB antagonist PDTC did not affect IL-1β-evoked tactile allodynia. In conclusion, our data provide additional evidence that RN IL-1β is involved in pain modulation, and that it exerts a facilitatory effect by activating the JAK/STAT3 and JNK signaling pathways.

Authors+Show Affiliations

Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, China. Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China.Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, China. Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China.Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, China.Department of Pathology, Xi'an Jiaotong University Health Science Center, Xi'an, China.Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, China. Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30216497

Citation

Guo, Yi-Jie, et al. "Red Nucleus Interleukin-1β Evokes Tactile Allodynia Through Activation of JAK/STAT3 and JNK Signaling Pathways." Journal of Neuroscience Research, vol. 96, no. 12, 2018, pp. 1847-1861.
Guo YJ, Li HN, Ding CP, et al. Red nucleus interleukin-1β evokes tactile allodynia through activation of JAK/STAT3 and JNK signaling pathways. J Neurosci Res. 2018;96(12):1847-1861.
Guo, Y. J., Li, H. N., Ding, C. P., Han, S. P., & Wang, J. Y. (2018). Red nucleus interleukin-1β evokes tactile allodynia through activation of JAK/STAT3 and JNK signaling pathways. Journal of Neuroscience Research, 96(12), 1847-1861. https://doi.org/10.1002/jnr.24324
Guo YJ, et al. Red Nucleus Interleukin-1β Evokes Tactile Allodynia Through Activation of JAK/STAT3 and JNK Signaling Pathways. J Neurosci Res. 2018;96(12):1847-1861. PubMed PMID: 30216497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Red nucleus interleukin-1β evokes tactile allodynia through activation of JAK/STAT3 and JNK signaling pathways. AU - Guo,Yi-Jie, AU - Li,Hao-Nan, AU - Ding,Cui-Ping, AU - Han,Shui-Ping, AU - Wang,Jun-Yang, Y1 - 2018/09/14/ PY - 2018/04/18/received PY - 2018/08/16/revised PY - 2018/08/20/accepted PY - 2018/9/15/pubmed PY - 2019/12/4/medline PY - 2018/9/15/entrez KW - RRID:AB_10711040 KW - RRID:AB_10973183 KW - RRID:AB_2139685 KW - RRID:AB_2491009 KW - RRID:AB_2722762 KW - RRID:AB_308787 KW - RRID:AB_331772 KW - RRID:AB_477010 KW - RRID:AB_93253 KW - RRID:nif-0000-30467 KW - interleukin-1β KW - neuropathic pain KW - red nucleus KW - signaling pathway SP - 1847 EP - 1861 JF - Journal of neuroscience research JO - J Neurosci Res VL - 96 IS - 12 N2 - We previously reported that interleukin-1β (IL-1β) in the red nucleus (RN) is involved in pain modulation and exerts a facilitatory effect in the development of neuropathic pain. Here, we explored the actions of signaling pathways, including the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-κB (NF-κB) pathways, on RN IL-1β-mediated pain modulation. After a single dose of recombinant rat IL-1β (rrIL-1β, 10 ng) injected into the RN in normal rats, a tactile allodynia was evoked in the contralateral but not ipsilateral hindpaw, commencing 75 min and peaking 120 min postinjection. Up-regulated protein levels of phospho-STAT3 (p-STAT3) and p-JNK were observed in the RN 120 min after rrIL-1β injection, the increases of p-STAT3 and p-JNK were blocked by anti-IL-1β antibody. However, the expression levels of p-ERK, p-p38 MAPK, and NF-κB in the RN were not affected by rrIL-1β injection. RN neurons and astrocytes contributed to IL-1β-evoked up-regulation of p-STAT3 and p-JNK. Further studies demonstrated that injection of the JAK2 antagonist AG490 or JNK antagonist SP600125 into the RN 30 min prior to the administration of rrIL-1β could completely prevent IL-1β-evoked tactile allodynia, while injection of the ERK antagonist PD98059, p38 MAPK antagonist SB203580, or NF-κB antagonist PDTC did not affect IL-1β-evoked tactile allodynia. In conclusion, our data provide additional evidence that RN IL-1β is involved in pain modulation, and that it exerts a facilitatory effect by activating the JAK/STAT3 and JNK signaling pathways. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/30216497/Red_nucleus_interleukin_1β_evokes_tactile_allodynia_through_activation_of_JAK/STAT3_and_JNK_signaling_pathways_ L2 - https://doi.org/10.1002/jnr.24324 DB - PRIME DP - Unbound Medicine ER -