کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6450739 1416138 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the inflammasome in macrophages
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the inflammasome in macrophages
چکیده انگلیسی


- A novel library of chitosans with distinct structural properties was generated.
- Only chitosans containing ≥3 kDa block glucosamine induced macrophage cytokines.
- Low chitosan doses induced type 1 interferon and IL-1ra and CXCL10 production.
- High chitosan doses activated the inflammasome and IL-1β and PGE2 production.
- Chitosan-mediated cytokine responses depended on lysosomal rupture.

Chitosan is a family of glucosamine and N-acetyl glucosamine polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to a novel library of twenty chitosans with controlled degree of deacetylation (DDA, 60-98%), molecular weight (1 to >100 kDa), and acetylation pattern (block vs. random). Specific chitosan preparations (10 or 190 kDa 80% block DDA and 3, 5, or 10 kDa 98% DDA) either induced macrophages to release CXCL10 and IL-1ra at 5-50 μg/mL, or activated the inflammasome to release IL-1β and PGE2 at 50-150 μg/mL. Chitosan induction of these factors required lysosomal acidification. CXCL10 production was preceded by lysosomal rupture as shown by time-dependent co-localization of galectin-3 and chitosan and slowed autophagy flux, and specifically depended on IFN-β paracrine activity and STAT-2 activation that could be suppressed by PGE2. Chitosan induced a type I IFN paracrine response or inflammasome response depending on the extent of lysosomal rupture and cytosolic foreign body invasion. This study identifies the structural motifs that lead to chitosan-driven cytokine responses in macrophages and indicates that lysosomal rupture is a key mechanism that determines the endogenous release of either IL-1ra or IL-1β.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 129, June 2017, Pages 127-138
نویسندگان
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