Butyrate is an anti tumor agent, so it is cytotoxic. Therefore, the intranasal delivery of butyrate may LEE011? be harmful to the nasal mucosa. Furthermore, the nasal absorption of butyrate by each mouse would be different due to the influence of respiration. Because of these, we considered that intragastric injection of butyrate might be a more appro priate form of administration in this study. Moreover, our results showed that this form of administration was feasible and effective. In addition, we only investigated the protective effect of butyrate on ALI on the condition that butyrate was administrated before LPS exposure, which was not often possible clinically. Given that pro inflammatory cytokines TNF a and IL 1b were released within hours after onset of ALI, early butyrate treatment after LPS exposure should be protective.

Thus, in the further study, we will evaluate the protective effect of delayed butyrate treatment on ALI, and also investigate the optimal time window and dose of delayed butyrate treatment. In conclusion, we have provided the first evidence that pretreatment of butyrate significantly attenuated pul monary inflammation in LPS induced ALI in mice. Thus, they might be useful in situations where current anti inflammatory therapies are unsatisfactory. Background Chronic obstructive pulmonary disease is an inflammatory lung disease characterized by a progressive and largely irreversible airflow obstruction, which involves structural changes of the lung, including emphy sema and small airway remodelling.

Small airway remodelling in COPD is characterized by adventitial fibrosis and mucus cell hyperplasia, and may involve increased airway smooth muscle mass, particu larly in severe disease. Small airway remodelling may contribute to the reduced lung function as well as to persistent airway hyperresponsiveness, which is present in most of the patients. Tobacco smoke exposure is considered to be the most important risk factor for COPD in developed countries. Lipopolysaccharide a constituent of the outer wall of gram negative bacteria and a contaminant of tobacco smoke, organic dust and environmental pollution has been implicated in the development and progression of various pulmonary diseases, including COPD. Cigarette smoke and LPS have previously been shown to induce features of airway remodelling in animal models, including airway wall thickening, increased ASM mass, goblet cell hyperplasia and collagen deposition.

Although the mechanisms involved in the development and progression of small airway remodelling in COPD Anacetrapib are largely unknown, chronic inflammation of the airways is presumably of major importance. This is indicated by persistent infiltration of inflammatory cells, including macrophages, neutrophils and T and B lymphocytes, in the airway wall, which is correlated with the severity of airflow obstruction.