Resistin-like molecule alpha1 (Fizz1) recruits lung dendritic cells without causing pulmonary fibrosis

Respiratory Research

Thomas R Korfhagen¹  William D Hardie²  Joseph A Kitzmiller¹  Cynthia Davidson²  Stephanie Schmidt²  Katy R Davis¹  Ramakrishna Edukulla²  Satish K Madala² 

[1] Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;Division of Pulmonary Medicine, Cincinnati, OH, USA

关键词: Retnla;    Fizz1;    Silicosis;    Bleomycin;    Pulmonary fibrosis;   

Others  :  796709
DOI  :  10.1186/1465-9921-13-51

 received in 2012-02-29, accepted in 2012-06-06,  发布年份 2012

【 摘 要 】

Background

Resistin-like molecule alpha or found in inflammatory zone protein (Fizz1) is increased in pulmonary epithelial cells and also in limited amounts by other lung cells during various lung injuries and fibrosis. However, the direct role of Fizz1 produced in the pulmonary epithelium has not been determined.

Methods

Fizz1 Transgenic mice (CCSP/Fizz1) were generated that overexpress Fizz1 in the lung epithelium under the control of a doxycycline (Dox) inducible lung epithelial cell specific promoter Scgb1a1 (Clara cell secretory protein, CCSP). Histology and FACS analysis of lung cells were used to identify the direct effects of Fizz1 in the transgenic mice (Dox treated) when compared with control (CCSP/-) mice. Intratracheal bleomycin sulfate or silica in saline and saline alone were used to study the role of Fizz1 during bleomycin- and silica-induced pulmonary fibrosis in CCSP/Fizz1 and CCSP/- mice. Weight change, pulmonary inflammation, and fibrosis were assessed 10 days post bleomycin or 28 days post silica challenge.

Results

When CCSP/Fizz1 mice were fed Dox food, elevated Fizz1 protein was detected in lung homogenates by western blot. Lungs of mice in which Fizz1 was induced in the epithelium contained increased lung cells staining for CD11c and F4/80 by FACS analysis consistent with increased dendritic cells however, no changes were observed in the percentage of interstitial macrophages compared to CCSP/- controls. No significant changes were found in the lung histology of CCSP/Fizz1 mice after up to 8 weeks of overexpression compared to CCSP/- controls. Overexpression of Fizz1 prior to challenge or following challenge with bleomycin or silica did not significantly alter airway inflammation or fibrosis compared to control mice.

Conclusions

The current study demonstrates that epithelial cell derived Fizz1 is sufficient to increase the bone-marrow derived dendritic cells in the lungs, but it is not sufficient to cause lung fibrosis or alter chemical or particle-induced fibrosis.

【 授权许可】

   
2012 Madala et al.; licensee BioMed Central Ltd.

【 图 表 】

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