[Blocking IL-17A protects against lung injury-induced pulmonary fibrosis through promoting the activation of p50NF-kappaB].

Aug 25, 2012Yao xue xue bao = Acta pharmaceutica Sinica

Blocking IL-17A may protect against lung scarring after injury by activating p50NF-kappaB

AI simplified

Abstract

Targeting IL-17A significantly decreases collagen deposition and improves survival rates in mice following acute lung injury.

Blocking IL-17A prevents the development of lung inflammation and fibrosis after injury.
Treatment led to reduced levels of hydroxyproline and collagen in lung tissue.
Targeting IL-17A resulted in decreased expression of pro-fibrotic cytokines, including TGF-beta1 and IL-13.
Increased levels of anti-fibrotic factors, such as IFN-gamma, were observed following IL-17A blockade.
IL-17A antagonism altered the activation of inflammation-related proteins, favoring resolution over prolonged inflammation.

AI simplified

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.

Abstract

Related papers

what lands in your inbox each week: