STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

Song, Zhenpeng, Xiong, Bingrui, Zheng, Hua, Manyande, Anne, Guan, Xuehai, Cao, Fei, Ren, Lifang, Zhou, Yaqun, Ye, Dawei and Tian, Yuke (2016) STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia. Brain, Behavior and Immunity, 60. pp. 161-173. ISSN 0889-1591

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Abstract

Major histocompatibility class II (MHC II)-specific activation of CD4+ T helper cells generates specific and persistent adaptive immunity against tumors. Emerging evidence demonstrates that MHC II is also involved in basic pain perception; however, little is known regarding its role in the development of cancer-induced bone pain (CIBP). In this study, we demonstrate that MHC II expression was markedly induced on the spinal microglia of CIBP rats in response to STAT1 phosphorylation. Mechanical allodynia was ameliorated by either pharmacological or genetic inhibition of MHC II upregulation, which was also attenuated by the inhibition of pSTAT1 and pERK but was deteriorated by intrathecal injection of IFNγ. Furthermore, inhibition of ERK signaling decreased the phosphorylation of STAT1, as well as the production of MHC II in vivo and in vitro. These findings suggest that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia.

Item Type: Article
Additional Information: © 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: Bone cancer pain; Microglia; Major histocompatibility complex class II; ERK; STAT1
Subjects: Medicine and health > Clinical medicine
Psychology
Depositing User: Anne Manyande
Date Deposited: 17 Oct 2016 16:39
Last Modified: 03 Jan 2017 09:33
URI: http://repository.uwl.ac.uk/id/eprint/2919

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