Blocking IL-17A protects against lung injury-induced pulmonary fibrosis through promoting the activation of p50NF-kappaB.
- Author:
Su MI
1
;
Zhe LI
;
Hong LIU
;
Zhuo-Wei HU
;
Fang HUA
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Acute Lung Injury;
chemically induced;
complications;
Animals;
Bleomycin;
Collagen;
metabolism;
Hydroxyproline;
metabolism;
Interleukin-13;
metabolism;
Interleukin-17;
antagonists & inhibitors;
metabolism;
Male;
Mice;
Mice, Inbred C57BL;
NF-kappa B p50 Subunit;
metabolism;
Pneumonia;
etiology;
metabolism;
Pulmonary Fibrosis;
etiology;
metabolism;
prevention & control;
Random Allocation;
Transcription Factor RelA;
metabolism;
Transforming Growth Factor beta1;
metabolism;
Up-Regulation
- From:
Acta Pharmaceutica Sinica
2012;47(6):739-744
- CountryChina
- Language:Chinese
-
Abstract:
This study is to determine the preventive effect and mechanism of targeting IL-17A on pulmonary inflammation and fibrosis after acute lung injury. Mice were treated with anti-IL-17A antibody on the day 7 and sacrificed on the day 14 after bleomycin lung injury. The pulmonary inflammatory status and the deposition of collagen were measured by HE and Sirius stains staining. The contents of hydroxyproline and collagen were measured by using commercial kits. The survival rate of mice was calculated by Kaplan-Meier methods. The inflammatory cytokines in bronchoalveolar lavage fluid were measured by ELISA and the expressions of inflammation-related molecules were detected by Western blotting assay. Targeting of IL-17A could prevent the development of lung inflammation, decrease collagen deposition and the contents of hydroxyproline, and protect against the development of pulmonary fibrosis, which together led to an increase in the animal survival. Moreover, blocking IL-17A decreased the expression ofpro-fibrotic cytokines such as IL-17A, TGF-beta1 and IL-13; increased the expression of anti-fibrotic or anti-inflammatory factors such as IFN-gamma, COX-2, 5-LOX, 15-LOX. Indeed, IL-17A antagonism suppressed the activation of pro-inflammatory p65NF-kappaB but enhanced the activation of pro-resolving p50NF-kappaB. In conclusion, that blockade of IL-17A prevents the development of pulmonary fibrosis from acute lung injury, is because blocking IL-17A may prevent acute inflammation converting to chronic inflammation.
