کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2183911 1550302 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of Toll-like receptor responses for sepsis pathogenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Role of Toll-like receptor responses for sepsis pathogenesis
چکیده انگلیسی

Sepsis remains a serious clinical problem because of high patient morbidity and mortality. Despite significant advances in critical care, there is still no efficient causal therapy applicable to patients indicating the need to further elucidate the molecular pathways leading to the immunopathology of sepsis. The importance of Toll-like receptors (TLR) for the induction of immune responses against sepsis was demonstrated in humans exhibiting polymorphisms in TLR genes and in animal models using genetically modified mouse strains. Because of the clinical heterogeneity in human sepsis and the complex pathomechanisms underlying sepsis, several different animal models might be used to cover the diverse features of sepsis. TLR receptors induce signaling through the adapter proteins MyD88 and TRIF. TLR signaling is tightly controlled at different steps of the signaling cascade by series of regulatory proteins. Using a model of severe polymicrobial septic peritonitis we could show that single TLRs are dispensable for the induction of innate immune responses under those conditions. However, genetic ablation of MyD88 or TRIF/type-I interferon signaling pathways prevented hyper-inflammation and attenuated the pathogenic consequences of sepsis indicating that dampening common signaling pathways may create a moderate signal strength which is associated with favorable immune responses. Therefore, broad knowledge about the regulation of TLR-induced signaling pathways may further elucidate the immune mechanisms during sepsis and targeting of TLR adapter molecules may provide a new therapeutic strategy against severe sepsis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunobiology - Volume 212, Issues 9–10, 18 January 2008, Pages 715–722
نویسندگان
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