Details

Autor(en) / Beteiligte

• Le, Thanh-Thuy T
• Karmouty-Quintana, Harry
• Melicoff, Ernestina
• Le, Thanh-Truc T
• Weng, Tingting
• Chen, Ning-Yuan
• Pedroza, Mesias
• Zhou, Yang
• Davies, Jonathan
• Philip, Kemly
• Molina, Jose
• Luo, Fayong
• George, Anuh T
• Garcia-Morales, Luis J
• Bunge, Raquel R
• Bruckner, Brian A
• Loebe, Matthias
• Seethamraju, Harish
• Agarwal, Sandeep K
• Blackburn, Michael R

Titel

Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis

Ist Teil von

• The Journal of immunology (1950), 2014-10, Vol.193 (7), p.3755-3768

Ort / Verlag

United States: AAI

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.