NF B is a protein transcription factor that functions to enhance the transcription of www.selleckchem.com/products/PF-2341066.html a variety of genes, including cytokines and growth factors, adhesion molecules, immunoreceptors, and acute phase proteins. Upon activation by LPS, NF B is required for maximal tran scription of many cytokines, including tumor necrosis factor a, interleukin 1b, IL 6, and IL 8, which are thought to be important in the generation of ALI. These cytokines and chemokines contribute to the vigorous recruitment of neutrophils in lung. Therefore, ALI is substantially caused by excessive neutrophil and cytokine mediated inflammation. Despite advancement in understanding the pathophysiology of ALI ARDS and improved therapy methods, however, mortality rates of ALI ARDS are around 40%. Histone deacetylases regulate gene expres sion.

In general, inhibitors of HDACs result in a non specific increase in gene expression. Therefore, they are considered as a new class of therapeutic agents for the treatment of tumor. Agents such as trichostatin A or suberoylanilide hydroxamic acid induce differentiation and or apoptosis of transformed cells in vitro and inhibit tumor growth in vivo. An unexpected effect of HDAC inhibitors, however, was revealed by recent studies indicating that they are able to suppress transcription and reduce inflammatory cyto kines in models of autoimmune and inflammatory dis eases. Butyrate, a HDAC inhibitor, is a short chain fatty acid derived from bacterial metabolism of dietary fibers in the colon and produces cell cycle arrest, differ entiation and or apoptosis of colorectal cancer cells in vitro.

Previous study has shown that butyrate reduced inflammation in Crohns disease through NF B inhibition. To date, unfortunately, the protective role of HDAC inhibitors in ALI is not well characterized. The aims of this study were to investigate whether butyrate reduces inflammation in LPS induced ALI in mice and to determine whether the protective effect is produced by suppression of inflammatory cytokines production and NF B activation. Materials and methods Animals and Reagents Male BALB C mice weighing 20 25 g were purchased from the Animal Center of the Fourth Military Medical University. All animals were allowed to take food and tap water ad libitum. All procedures were in accordance with the Declaration of Helsinki of the World Medical Association.

The protocols were also approved by the Institutional Animal Care and Use Committee of the Fourth Military Medical University Tangdu Hospital. LPS and butyrate were obtained from Sigma Chemical Company, and were respectively dissolved in saline. Enzyme linked immunosorbent assay kits of TNF a, IL 1b, myeloperoxidase Anacetrapib and nitric oxide were purchased from R D Corporation. Antibodies speci fic for total NF B p65, Lamin B and b actin were obtained from the Wuhan Boster Biological Technology, Ltd.