کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7281023 | 1473919 | 2015 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing](/preview/png/7281023.png)
چکیده انگلیسی
Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1 mg/kg) or intracerebroventricular (5 μg) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-1β and TNF-α genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1β promoter. ChIP and knock-down experiments showed that NF-κB subunit RelB was bound to the IL-1β promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 48, August 2015, Pages 205-221
Journal: Brain, Behavior, and Immunity - Volume 48, August 2015, Pages 205-221
نویسندگان
W. Schaafsma, X. Zhang, K.C. van Zomeren, S. Jacobs, P.B. Georgieva, S.A. Wolf, H. Kettenmann, H. Janova, N. Saiepour, U.-K. Hanisch, P. Meerlo, P.J. van den Elsen, N. Brouwer, H.W.G.M. Boddeke, B.J.L. Eggen,