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Laboratory and Animal Investigations |

Anti-Tissue Remodeling Effects of Corticosteroids*: Fluticasone Propionate Inhibits Fibronectin Expression in Fibroblasts

Rade Tomic, MD; Charles C. Lassiter, MD; Jeffrey D. Ritzenthaler, MA; Hilda N. Rivera, BA; Jesse Roman, MD
Author and Funding Information

*From the Department of Medicine (Drs. Tomic, Lassiter, and Roman, and Mr. Ritzenthaler), Division of Pulmonary, Allergy and Critical Care Medicine; and Atlanta VA Medical Center and Emory University School of Medicine (Ms. Rivera), Atlanta, GA.

Correspondence to: Jesse Roman, MD, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michael St, Suite 205-M, Atlanta, GA 30322; e-mail: jroman@emory.edu



Chest. 2005;127(1):257-265. doi:10.1378/chest.127.1.257
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Objectives: Tissue remodeling often accompanies diseases such as COPD that are caused by or aggravated by tobacco exposure. Inhaled or systemic corticosteroids are frequently used for the treatment of these illnesses, and their beneficial effects are often ascribed to their anti-inflammatory properties. However, their role in tissue remodeling remains unclear. This study was designed to evaluate the role of corticosteroids in matrix expression in vitro.

Design: We investigated the effects of the corticosteroid fluticasone propionate (FP) on the production of fibronectin by fibroblasts before and after stimulation by nicotine, a plant alkaloid found in tobacco. Fibronectin is an extracellular matrix glycoprotein found elevated in the alveolar lining fluid and airway walls of subjects with obstructive lung disease, and is considered a marker of tissue remodeling after injury.

Results: FP, 1 μmol/L, inhibited the expression of fibronectin messenger RNA and protein in unstimulated NIH-3T3 cells and primary lung fibroblasts, as well as in fibroblasts stimulated with nicotine. The inhibitory effect of FP occurred at the level of gene transcription as demonstrated in lung fibroblasts expressing a construct containing the human fibronectin promoter connected to a luciferase reporter gene, but posttranscriptional effects also appeared involved. Electrophoresis mobility gel shift assays revealed that FP inhibited phosphorylation and DNA binding by the cyclic adenosine monophosphate response element binding protein, a transcription factor required for constitutive and nicotine-induced fibronectin expression.

Conclusions: Together, these data suggest that FP could diminish lung tissue remodeling by inhibiting the production of fibronectin in lung fibroblasts.

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