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Publication : Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production.

First Author  Horio Y Year  2017
Journal  PLoS One Volume  12
Issue  7 Pages  e0180742
PubMed ID  28704475 Mgi Jnum  J:250609
Mgi Id  MGI:5916634 Doi  10.1371/journal.pone.0180742
Citation  Horio Y, et al. (2017) Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production. PLoS One 12(7):e0180742
abstractText  PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation and remodeling of the lungs and airways result in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune modulator in various diseases. However, its role in the pathogenesis of pulmonary emphysema is unknown. This study investigates whether Gal-9 is involved in pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase (PPE)-induced emphysema model. MATERIALS AND METHODS: Gal-9 was administered to mice subcutaneously once daily from 1 day before PPE instillation to day 5. During the development of emphysema, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. Histological and cytological findings, concentrations of chemokines and matrix metalloproteinases (MMPs) in the BALF, and the influence of Gal-9 treatment on neutrophils were analyzed. RESULTS: Gal-9 suppressed the pathological changes of PPE-induced emphysema. The mean linear intercept (Lm) of Gal-9-treated emphysema mice was significantly lower than that of PBS-treated emphysema mice (66.1 +/- 3.3 mum vs. 118.8 +/- 14.8 mum, respectively; p < 0.01). Gal-9 decreased the number of neutrophils and levels of MMP-9, MMP-2 and tissue inhibitor of metalloproteinases (TIMP)-1 in the BALF. The number of neutrophils in the BALF correlated significantly with MMPs levels. Interestingly, Gal-9 pretreatment in vitro inhibited the chemotactic activity of neutrophils and MMP-9 production from neutrophils. Furthermore, in Gal-9-deficient mice, PPE-induced emphysema progressed significantly compared with that in wild-type (WT) mice (108.7 +/- 6.58 mum vs. 77.19 +/- 6.97 mum, respectively; p < 0.01). CONCLUSIONS: These results suggest that Gal-9 protects PPE-induced inflammation and emphysema by inhibiting the infiltration of neutrophils and decreasing MMPs levels. Exogenous Gal-9 could be a potential therapeutic agent for COPD.
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