title: Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response.
abstract: Ischemic stroke causes brain injury with activation of an inflammatory response that can contribute to clinical impairment. As a novel cytokine of the interleukin-1 (IL-1) family, IL-33 has been suggested to be involved in regulating pathophysiology and inflammatory responses in the central nervous system (CNS). However, the role and underlying mechanisms of IL-33 in ischemic stroke remain poorly understood. Here, adult male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) for stroke induction. The MCAO procedure resulted in the enhanced Th1 and Th17 immune responses from 6h after transient cerebral ischemia/reperfusion even up to day 3. Meanwhile, the protein and mRNA level of IL-33 expression was significantly decreased at 6h and 72 h, but not at 24h after MCAO. Moreover, recombinant mouse IL-33 administration substantially attenuated ischemic brain damage and neurological deficit at 24h and 72 h, but not at 6h after MCAO. Interestingly, the reduced CNS inflammation in IL-33-treated MCAO mice may be at least partly due to an induced immuno-shift of Th cells from Th1 to Th2 response and suppressing Th17 immune response. These findings demonstrate that IL-33 can play a protective role after MCAO and may be a new target for therapy of ischemic stroke.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xiongwenwu@hotmail.com.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004926:Escherichia coli; D020244:Infarction, Middle Cerebral Artery; D000067596:Interleukin-33 / Q000008:administration & dosage / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology; D058408:Th1-Th2 Balance / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects / Q000502:physiology*; D018418:Th2 Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins
keywords: IL-33; Ischemic stroke; MCAO; Th1/Th2 balance; Th17 immune response