کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6272705 1614786 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pivotal role of cerebral interleukin-23 during immunologic injury in delayed cerebral ischemia in mice
ترجمه فارسی عنوان
نقش مؤثر اینترلوکین 23 مغزی در طی آسیب ایمونولوژیک در وازچه ایسایمی مغزی در موش سوری
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


- IL-23p19 knockdown improves neurological scores and reduces infarct volume.
- IL-23p19 knockdown reduced the expression of IL-17.
- IL-23p19 knockdown increased IFN-γ expression.
- IL-23p19 knockdown had no impact on cytokine IL-4 expression.
- IL-23p19 knockdown increased Foxp3 expression.

BackgroundInterleukin-23 (IL-23) is required for T helper 17 (Th17) cell responses and IL-17 production in ischemic stroke. We previously showed that the IL-23/IL-17 axis aggravates immune injury after cerebral infarction in mice. However, IL-23 might activate other cytokines and transcription factor forkhead box P3 (Foxp3) production in cerebral ischemia. We aimed to determine whether IL-23p19 knockdown prevents cerebral ischemic injury by reducing ischemic-induced inflammation.MethodsIschemic stroke models were established by permanent middle cerebral arterial occlusion (pMCAO) in male C57BL/6 mice. In vivo gene knockdown was achieved by intravenous delivery of lentiviral vectors (LVs) encoding IL-23p19 short hairpin RNA (LV-IL-23p19 shRNA). Enzyme-linked immunoassay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed inhibitory efficiency. Behavioral deficits were evaluated by adhesive-removal somatic-sensory test. Brain infarct volume was measured at day 5 after pMCAO by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Expression of IL-17, IL-4, interferon (IFN)-γ and Foxp3 in ischemic brain tissues were detected by qRT-PCR and Western blotting, respectively. Additionally, immunohistochemical staining located cytokines in ischemic brain tissues.ResultsRNA interference knockdown of IL-23p19 resulted in improved neurological function and reduced infarct volume. IL-23p19 knockdown suppressed IL-17 gene and protein expression. Moreover, IL-23p19 deficiency enhanced IFN-γ and Foxp3 expressions in delayed cerebral ischemic mice, and did not impact IL-4 expression. Immunohistochemical staining showed that IL-17, IL-4, IFN-γ and Foxp3-positive cells were located around ischemic lesions of the ipsilateral hemisphere.ConclusionsIL-23p19 knockdown prevents delayed cerebral ischemic injury by dampening the ischemia-induced inflammation, and is a promising approach for clinically managing ischemic stroke.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 290, 2 April 2015, Pages 321-331
نویسندگان
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