کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3885822 1249525 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
‘Endotoxin tolerance’: TNF-α hyper-reactivity and tubular cytoresistance in a renal cholesterol loading state
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
‘Endotoxin tolerance’: TNF-α hyper-reactivity and tubular cytoresistance in a renal cholesterol loading state
چکیده انگلیسی

The term ‘endotoxin tolerance’ defines a state in which prior endotoxin (lipopolysaccharide (LPS)) exposure induces resistance to subsequent LPS attack. However, its characteristics within kidney have not been well defined. Hence, this study tested the impact of LPS ‘preconditioning’ (LPS-PC; 18 or 72 h earlier) on: (i) selected renal inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), Toll-like receptor 4 (TLR4); protein or mRNA); (ii) cholesterol homeostasis (a stress reactant); and (iii) isolated proximal tubule (PT) vulnerability to hypoxia or membrane cholesterol (cholesterol oxidase/esterase) attack. Two hours post LPS injection, LPS-PC mice manifested reduced plasma TNF-α levels, consistent with systemic LPS tolerance. However, in kidney, paradoxical TNF-α hyper-reactivity (protein/mRNA) to LPS existed, despite normal TLR4 protein levels. PT TNF-α levels paralleled renal cortical results, implying that PTs were involved. LPS-PC also induced: (i) renal cortical iNOS, IL-10 (but not MCP-1) mRNA hyper-reactivity; (ii), PT cholesterol loading, and (iii) cytoresistance to hypoxia and plasma membrane cholesterol attack. A link between cholesterol homeostasis and cell LPS responsiveness was suggested by observations that cholesterol reductions in HK-2 cells (methylcyclodextrin), or reductions in HK-2 membrane fluidity (A2C), blunted LPS-mediated TNF-α/MCP-1 mRNA increases. In sum: (i) systemic LPS tolerance can be associated with renal hyper-responsiveness of selected components within the LPS signaling cascade (e.g., TNF-α, iNOS, IL-10); (ii) PT cytoresistance against hypoxic/membrane injury coexists; and (iii) LPS-induced renal/PT cholesterol accumulation may mechanistically contribute to each of these results.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 71, Issue 6, 2 March 2007, Pages 496–503
نویسندگان
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