کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
329372 1433622 2010 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
S100B/RAGE-dependent activation of microglia via NF-κB and AP-1: Co-regulation of COX-2 expression by S100B, IL-1β and TNF-α
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
S100B/RAGE-dependent activation of microglia via NF-κB and AP-1: Co-regulation of COX-2 expression by S100B, IL-1β and TNF-α
چکیده انگلیسی

Extracellular S100B is known to affect astrocytic, neuronal and microglial activities, with different effects depending on its concentration. Whereas at relatively low concentrations S100B exerts trophic effects on neurons and astrocytes, at relatively high concentrations the protein causes neuronal apoptosis and activates astrocytes and microglia, thus potentially representing an endogenous factor implicated in neuroinflammation. We have reported that RAGE ligation by S100B in BV-2 microglia results in the upregulation of expression of the pro-inflammatory cyclo-oxygenase 2 (COX-2) via parallel Ras-Cdc42-Rac1-dependent activation of c-Jun NH2 terminal protein kinase (JNK) and Ras-Rac1-dependent stimulation of NF-κB transcriptional activity. We show here that: (1) S100B also stimulates AP-1 transcriptional activity in microglia via RAGE-dependent activation of JNK; (2) S100B upregulates IL-1β and TNF-α expression in microglia via RAGE engagement; and (3) S100B/RAGE-induced upregulation of COX-2, IL-1β and TNF-α expression requires the concurrent activation of NF-κB and AP-1. We also show that S100B synergizes with IL-1β and TNF-α to upregulate on COX-2 expression in microglia. Given the crucial roles of COX-2, IL-1β and TNF-α in the inflammatory response, we propose that, by engaging RAGE, S100B might play an important role in microglia activation in the course of brain damage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 31, Issue 4, April 2010, Pages 665–677
نویسندگان
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