In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 9 ( 2009-05-01), p. 5374-5381
Abstract:
Despite an increase in the knowledge of mechanisms and mediators involved in pulmonary fibrosis, there are no successful therapeutics available. Lipoxins (LX) and their 15-epimers, aspirin-triggered LX (ATL), are endogenously produced eicosanoids with potent anti-inflammatory and proresolution effects. To date, few studies have been performed regarding their effect on pulmonary fibrosis. In the present study, using C57BL/6 mice, we report that bleomycin (BLM)-induced lung fibrosis was prevented by the concomitant treatment with an ATL synthetic analog, ATLa, which reduced inflammation and matrix deposition. ATLa inhibited BLM-induced leukocyte accumulation and alveolar collapse as evaluated by histology and morphometrical analysis. Moreover, Sirius red staining and lung hydroxyproline content showed an increased collagen deposition in mice receiving BLM alone that was decreased upon treatment with the analog. These effects resulted in benefits to pulmonary mechanics, as ATLa brought to normal levels both lung resistance and compliance. Furthermore, the analog improved mouse survival, suggesting an important role for the LX pathway in the control of disease establishment and progression. One possible mechanism by which ATLa restrained fibrosis was suggested by the finding that BLM-induced myofibroblast accumulation/differentiation in the lung parenchyma was also reduced by both simultaneous and posttreatment with the analog (α-actin immunohistochemistry). Interestingly, ATLa posttreatment (4 days after BLM) showed similar inhibitory effects on inflammation and matrix deposition, besides the TGF-β level reduction in the lung, reinforcing an antifibrotic effect. In conclusion, our findings show that LX and ATL can be considered as promising therapeutic approaches to lung fibrotic diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.0802259
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
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