ATLa, an Aspirin-Triggered Lipoxin A4 Synthetic Analog, Prevents the Inflammatory and Fibrotic Effects of Bleomycin-Induced Pulmonary Fibrosis

摘要: Despite an increase in the knowledge of mechanisms and mediators involved pulmonary fibrosis, there are no successful therapeutics available. Lipoxins (LX) their 15-epimers, aspirin-triggered LX (ATL), endogenously produced eicosanoids with potent anti-inflammatory proresolution effects. To date, few studies have been performed regarding effect on fibrosis. In present study, using C57BL/6 mice, we report that bleomycin (BLM)-induced lung fibrosis was prevented by concomitant treatment ATL synthetic analog, ATLa, which reduced inflammation matrix deposition. ATLa inhibited BLM-induced leukocyte accumulation alveolar collapse as evaluated histology morphometrical analysis. Moreover, Sirius red staining hydroxyproline content showed increased collagen deposition mice receiving BLM alone decreased upon analog. These effects resulted benefits to mechanics, brought normal levels both resistance compliance. Furthermore, analog improved mouse survival, suggesting important role for pathway control disease establishment progression. One possible mechanism restrained suggested finding myofibroblast accumulation/differentiation parenchyma also simultaneous posttreatment (alpha-actin immunohistochemistry). Interestingly, (4 days after BLM) similar inhibitory deposition, besides TGF-beta level reduction lung, reinforcing antifibrotic effect. conclusion, our findings show can be considered promising therapeutic approaches fibrotic diseases.