title: STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia.
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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pain Medicine, Binzhou Medical University Hospital, Binzhou 256600, China.
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Bingrui
authors.initials: B
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: School of Human and Social Sciences, University of West London, Middlesex TW8 9GA, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Manyande
authors.affiliation: Department of Anesthesiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: dy0711@gmail.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yktian@tjh.tjmu.edu.cn.
authors.forename: Yuke
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D000072716:Cancer Pain / Q000378:metabolism; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism; D007278:Injections, Spinal / Q000379:methods; D020935:MAP Kinase Signaling System / Q000502:physiology; D017628:Microglia / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat
keywords: Bone cancer pain; ERK; Major histocompatibility complex class II; Microglia; STAT1