کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8550381 1562030 2018 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Manganese exposure facilitates microglial JAK2-STAT3 signaling and consequent secretion of TNF-a and IL-1β to promote neuronal death
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Manganese exposure facilitates microglial JAK2-STAT3 signaling and consequent secretion of TNF-a and IL-1β to promote neuronal death
چکیده انگلیسی
Chronic manganese (Mn) exposure can lead to neuroinflammation and neurological deficit, which resemble idiopathic Parkinson's disease (IPD). However, the precise mechanisms underlying Mn exposure-induced neurotoxicity remain incompletely understood. Microglia can become hyperactivated and plays a vital role in neuroinflammation and consequent neurodegeneration in response to pro-inflammatory stimuli. In the present study, we found that HAPI microglial cells exhibited increased secretion of pro-inflammatory TNF-α and IL-1β following Mn exposure in dose- and time-dependent manners. In addition, we showed that Mn exposure could trigger the activation of JAK2/STAT3 signaling pathway in microglia. Notably, Mn-induced secretion of TNF-α and IL-1β was significantly attenuated by the treatment of JAK2 inhibitor. Finally, through incubating PC12 neuronal cells with Mn-treated microglial conditioned medium, we demonstrated that Mn-induced secretion of microglial TNF-α and IL-1β facilitated neuronal apoptosis. Thus, we speculate that Mn exposure might trigger JAK2-STAT3 signal pathway in microglia, leading to resultant neuroinflammation and neuronal loss.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 64, January 2018, Pages 195-203
نویسندگان
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