کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6164405 | 1249469 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The high-mobility group protein B1-Toll-like receptor 4 pathway contributes to the acute lung injury induced by bilateral nephrectomy
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
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چکیده انگلیسی
Acute lung injury and acute kidney injury are severe complications in critically ill patients and synergistically increase mortality in intensive care units. Organ cross-talk between the kidney and the lung has been implicated recently as amplifying injury in each organ. Here we sought to identify a possible mechanism of acute kidney injury-induced acute lung injury using a mouse bilateral nephrectomy model. Toll-like receptor 4 (TLR4)-mutant C3H/HeJ mice were more resistant to lung injury including neutrophil infiltration, increased neutrophil elastase activity, and vascular permeability caused by bilateral nephrectomy compared with TLR4-wild-type C3H/HeN mice 6Â h after surgery. High-mobility group protein B1 (HMGB1) is one agonist for TLR4. Its blood concentrations were increased significantly by bilateral nephrectomy. Blockade of HMGB1 by neutralizing antibody reduced neutrophil infiltration in TLR4-wild-type C3H/HeN but not in TLR4-mutant C3H/HeJ mice. However, HMGB1 blockade in a renal ischemia reperfusion model reduced pulmonary neutrophil infiltration independent from TLR4. Thus, an enhanced HMGB1-TLR4 pathway contributes to lung injury induced by bilateral nephrectomy and the other HMGB1-dependent pathway exists in pulmonary neutrophil infiltration caused by renal ischemia reperfusion. Targeting the HMGB1-TLR4 pathway might enable development of a new therapeutic strategy to improve the outcomes of severely ill patients with both acute lung and acute kidney injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 86, Issue 2, August 2014, Pages 316-326
Journal: Kidney International - Volume 86, Issue 2, August 2014, Pages 316-326
نویسندگان
Kent Doi, Tomoko Ishizu, Maki Tsukamoto-Sumida, Takahiro Hiruma, Tetsushi Yamashita, Emi Ogasawara, Yoshifumi Hamasaki, Naoki Yahagi, Masaomi Nangaku, Eisei Noiri,