ABSTRACT
Aim To investigate the effect of broneol on acute lung injury(ALI) induced by lipopolysaccharide (LPS). Methods Male C57 mice were randomly di-vided into saline group, model group, broneol group and dexamethasone group, then the ALI mouse model was induced by instilling intratracheally with LPS. The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6) and keratinocyte-de-rived cytokine (KC) were measured at 6h, 12h and 24h after instillation of LPS, and the pathological changes of lung were observed. Mice alveolar macro-phages (MHS) and epithelial cells (MLE-12) were stimulated by LPS. After the stimulation of 1h, 3h, 6h,9h, 12h, 24h, the levels of TNF-α and IL-6 in MHS cells and the contents of KC and macrophage in-flammatory protein-2 (MIP-2) in MLE-12 cells were measured. Results Broneol could inhibit the secre-tion of TNF-α,KC and IL-1β;the early effect of bro-neol on IL-6 was not obvious,but the later effect after the treatment of 24 hours was obvious. After LPS instil-lation 6h and 12h,Broneol could significantly improve lung tissue pathological changes. Broneol had no effect on TNF-α secretion of MHS cells, but it obviously af-fected IL-6 secretion in the later stage. In addition, broneol significantly inhibited KC and MIP2 secretion in MLE-12 cells at the later stage of LPS stimulation. Conclusions Broneol can protect LPS-induced acute lung injury. The mechanism may be related to the inhi-bition of the release of inflammatory factors,the activa-tion of inflammatory cells and the aggregation of neutro-phils.
ABSTRACT
cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc. This article reviews the recent progress on PDE4-targeted therapy for inflammatory diseases.