| High mobility group box 1 (HMGB1), a 30 kD non histone chromatin-associated protein, is extremely conserved across species. As a nuclear protein, HMGB1 stabilizes nucleosomes and allows bending of DNA that facilitates gene transcription. HMGBl was identified as a late mediator of endotoxin lethality released from monocytes/macrophages in 1999 by Wang H. et al. Recent investigations have showed that HMGB1 activated a cascade of proinflammatory cytokine release from monocytes/macrophages or neutrophils and produced acute inflammatory injury to the lungs. Acute lung injury (ALI) is a disease process characterized by diffuse inflammation in the lung parenchyma. There is more recent evidence that nitric oxide (NO) plays a significant role in the pathogenesis of ALI. Because alveolar macrophages (AMs) expressed an abundance of inducible nitric oxide synthase (iNOS) and were important sources of NO in inflamed lung. There still is no report on the actions of NO on HMGB1-induced ALI. The present research aims to observe whether iNOS in AMs is upregulated by HMGB1 and its relative molecular mechanisms and actions in HMGB1-induced ALI. The ultimate aims of this research is to supply more theoretical explanations for the pathogenesis of ALI. This research includes the following parts:1. Actions of iNOS expressed by AMs in HMGB1-induced ALIAlveolar macrophage or iNOS was inhibited by gadolinium chloride (GdCl3)intravenously or aminoguanidine (AG) intraperitoneally respectively to observe its role in ALI elicited by HMGB1 intratracheally in rats. In situ hybridization and... |
