Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10.
Lab Invest
; 95(12): 1353-62, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26367488
ABSTRACT
Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-α, IL-1ß, IL-6, transforming growth factor-ß1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymal-like mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peritônio
/
Terapia Genética
/
Interleucina-10
/
Fibrose Peritoneal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Lab Invest
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Japão