Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis.
J Immunol
; 193(7): 3755-68, 2014 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-25172494
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 y of diagnosis. IPF incidence and prevalence rates are increasing annually with few effective treatments available. Inhibition of IL-6 results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6Rα, or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sIL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice during the onset and progression of fibrosis. We demonstrated that protease-mediated cleavage from lung macrophages was important in production of sIL-6Rα. In vivo neutralization of sIL-6Rα attenuated pulmonary fibrosis in mice as seen by reductions in myofibroblasts, fibronectin, and collagen in the lung. In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. Taken together, these findings demonstrate that the production of sIL-6Rα from macrophages in the diseased lung contributes to IL-6 trans signaling that in turn influences events crucial in pulmonary fibrosis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar
/
Transducción de Señal
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Interleucina-6
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Macrófagos Alveolares
/
Receptores de Interleucina-6
/
Fibrosis Pulmonar Idiopática
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Immunol
Año:
2014
Tipo del documento:
Article