Therefore, the inhi bition of TNF a and IL 1b showed the reduction of pul monary injury kinase inhibitor Vandetanib in ALI induced by LPS in mice. In the present study, the concentrations of TNF a and IL 1b in BALF and the expression of NF B p65 in nucleus increased significantly after LPS administration, and reached their peak at 3 hours respectively. Pretreat ment of butyrate markedly reduced the concentrations of TNF a and IL 1b in BALF, and suppressed the expression of NF B p65 in nucleus. In addition, we also found that in ALI mice the elevated MPO activity, a specific granulocyte enzyme, was significantly reduced by butyrate pretreatment. Although neutrophils have beneficial actions in eradicating microbial infections, excessive neutrophil accumulation in lung contributes to the development of ALI.

The cytokines secreted by alveolar macrophages, such as TNF a and IL 1b, play a key role in neutrophil recruitment to the lung. There fore, the reduced neutrophils infiltration in lung by butyrate administration was partially due to its inhibi tory effect on cytokines production. In our study, we also found the reduced expression of NF B in cytoplasm due to the enhanced NF B nuclear translocation after LPS administration, which was mark edly inhibited by butyrate pretreatment. Previous study showed that butyrate pretreatment of a human colon cell line inhibited the TNF a induced nuclear translocation of the pro inflammatory transcrip tion factor NF B in part by preventing the complete degradation of I B a by reducing proteasome activity in the cell.

Moreover, butyrate decreased TNF produc tion and pro inflammatory cytokine mRNA expression by intestinal biopsies and lamina propria cells from Crohns disease patients, and abolished LPS induced expression of cytokines by peripheral blood mononuclear cells and transmigration of NF B from the cytoplasm to the nucleus. In the RAW 264. 7 murine macrophage cells stimulated by LPS, butyrate down regulated NO production and prevented the acti vation of NF B through the stabilization of I B a and I B b. These results observed in vitro suggested that the anti inflammatory effects of butyrate in ALI may primarily rely on inhibition of I B degradation, and consequently inhibiting the nuclear translocation of NF B and the production of cytokines regulated by NF B. Pulmonary edema is a life threatening condition that frequently leads to acute respiratory failure.

Injury to the alveolar epithelium can disrupt the integrity of the alveolar GSK-3 barrier or down regulate ion transport path ways, thus, reducing net alveolar fluid reabsorption and enhancing the extent of alveolar edema. Here we observed a significant reduction of pulmonary injury and edema in lungs of ALI mice treated by butyrate. Therefore, butyrate possessed the protective effect on ALI, which implied the clinical use of butyrate in future.