کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2512399 1118348 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis
چکیده انگلیسی

Sepsis is caused by an overwhelming immune response to bacterial infection. The discovery of high mobility group box 1 (HMGB1) as a late mediator of lethal sepsis has prompted investigation into the development of new therapeutics which specifically target this protein. Here, we show that chloroquine, an anti-malarial drug, prevents lethality in mice with established endotoxemia or sepsis. This effect is still observed even if administration of chloroquine is delayed. The protective effects of chloroquine were mediated through inhibition of HMGB1 release in macrophages, monocytes, and endothelial cells, thereby preventing its cytokine-like activities. As an inhibitor of autophagy, chloroquine specifically inhibited HMGB1-induced Iκ-B degradation and NF-κB activation. These findings define a novel mechanism for the anti-inflammatory effects of chloroquine and also suggest a new potential clinical use for this drug in the setting of sepsis.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 86, Issue 3, 1 August 2013, Pages 410–418
نویسندگان
, , , , , , , ,