title: Damage effect of interleukin (IL)-23 on oxygen-glucose-deprived cells of the neurovascular unit via IL-23 receptor.
abstract: Interleukin-23/interleukin-23 receptor (IL-23/IL-23R) has been implicated in many inflammatory diseases. Previous research mainly focused on its ability to induce IL-17 production from T cells. However, few studies have investigated its role in cerebral ischemic injury. The aim of our study was to explore the potential effect of IL-23 on cells of the neurovascular unit (NVU) under an oxygen-glucose deprivation (OGD) condition and the role of IL-23R in IL-23-mediated effect. OGD of primary cells of the NVU and permanent middle cerebral artery occlusion (pMCAO) were used to produce experimental stroke in vitro and in vivo, respectively. IL-23 and IL-23R were detected by immunohistochemistry and western blot in pMCAO mice. Metabolic viability of cultured cells was assessed by MTT assay. The cell-associated proteins (Bcl-2, AQP4 and ET-1) were determined by western blot and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining and western blot were used to detect the IL-23R expression. The results showed that the expression of IL-23/IL-23R was elevated in pMCAO mice. IL-23 could aggravate neuron damage, astrocyte swelling, and further impair the integrity of blood-brain barrier induced by OGD. In addition, the effect of IL-23 on cells of the NVU is mediated by IL-23R and is likely IL-23R-expression-level dependent. However, there are no such biological properties for the IL-23p19 subunit alone. Our study provides the first evidence that IL-23 has a toxic effect on cells of the NVU under OGD stress, which is mediated by IL-23R. These results not only help us better understand the role of IL-23/IL-23R in brain ischemia, but also provide a potential therapeutic target in stroke.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Zhong
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, Harbin Medical University Provincial Key Lab of Neurobiology, Harbin Medical University, Xuefu Road, 150081 Heilongjiang, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin, 150001 Heilongjiang, PR China. Electronic address: hydlgz1962@163.com.
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000172:deficiency*; D020244:Infarction, Middle Cerebral Artery; D053759:Interleukin-23 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D018123:Receptors, Interleukin / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D053759:Interleukin-23; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse; C000603137:interleukin-23 receptor, rat; D005947:Glucose
keywords: IL-23; IL-23R; cerebral ischemic injury; p19 subunit