کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10753483 | 1050341 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
CD47 does not mediate amyloid-β(1-42) protofibril-stimulated microglial cytokine release
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کلمات کلیدی
ProtofibrilsTNFαSEChexafluoroisopropanolCD47AβHFIPaCSFIL-1βInterleukin-1β - اینترلوکین-1βThT - بلهAlzheimer’s disease - بیماری آلزایمرAggregation - تجمعtumor necrosis factor α - تومور نکروز عامل αThioflavin T - تیوفلاوین TCytokines - سیتوکین هاartificial cerebrospinal fluid - مایع مغزی نخاعی مصنوعیMicroglia - میکروگلیاهاamyloid-β protein - پروتئین آمیوئید بتاAmyloid-beta protein - پروتئین آمیوئید بتاSize exclusion chromatography - کروماتوگرافی اندازهای طردی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Neuroinflammation triggered by accumulation of amyloid-β protein (Aβ) is a significant component of the Alzheimer's disease (AD) brain. Senile plaques composed of Aβ attract and activate microglia cells resulting in cytokine secretion and a proinflammatory environment. The mechanism by which Aβ activates microglia is complex and involves numerous cellular components. One receptor potentially involved in Aβ recognition and the ensuing microglia proinflammatory response is CD47. Since there is significant interest in soluble aggregated Aβ species, we sought to determine if CD47 plays a key role in microglia cytokine release stimulated by soluble Aβ(1-42) protofibrils. Pretreatment of primary murine microglia with the CD47 antagonist peptide 4N1K significantly and potently inhibited both tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) secretion stimulated by Aβ(1-42) protofibrils. 4N1K displayed toxicity to the microglia but only at concentrations much higher than the observed inhibition. Surprisingly, 4N1K also potently inhibited TNFα secretion triggered by lipopolysaccharide which is not known to signal through CD47. Treatment of the microglia with a neutralizing anti-CD47 antibody failed to block the Aβ protofibril response even though comparable samples were completely inhibited by 4N1K. Finally, Aβ(1-42) protofibrils stimulated similar levels of secreted TNFα production in both wild-type and CD47â/â microglia and 4N1K still potently inhibited the Aβ protofibril response even in the CD47â/â microglia. The overall findings demonstrated that the microglial proinflammatory response to Aβ(1-42) protofibril is not dependent on CD47 and that 4N1K exhibits CD47-independent inhibitory activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 454, Issue 1, 7 November 2014, Pages 239-244
Journal: Biochemical and Biophysical Research Communications - Volume 454, Issue 1, 7 November 2014, Pages 239-244
نویسندگان
Sanjib Karki, Michael R. Nichols,