Research Project
Grant-in-Aid for Young Scientists (B)
Acute lung injury (ALI) and acute kidney injury (AKI) are severe complications in critically ill patients. These two organ dysfunctions synergistically increase mortality in intensive care units. Organ cross-talk between the kidney and the lung has been suggested recently as amplifying each organ injury. This study was conducted to identify a possible mechanism of AKI-induced ALI using a mouse bilateral nephrectomy (BNx) model. Toll-like receptor 4 (TLR4)-mutant C3He/J mice were resistant to lung injury including neutrophil infiltration and increased neutrophil elastase (NE) activity caused by BNx. High-mobility group protein B1 (HMGB1) is one of the agonists for TLR4. Its blood concentrations were increased significantly by BNx. Blockade of HMGB1 by neutralizing antibody reduced lung injury not in TLR4-mutant C3He/J but in TLR4-wild type C3He/N mice. These data suggest that enhanced HMGB-1-TLR4 pathway contributes to lung injury induced by BNx. Targeting the HMGB-1-TLR4 pathway will enable development of a new therapeutic strategy to improve the outcome of severely ill patients with ALI and AKI.
All 2011 Other
All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (1 results)
Clin Exp Nephrol.
Volume: 15 Pages: 464-470
10029571491
