Studies suggest that corticosteroids might affect tissue remodeling

Friday, October 17th, 2014 No Commented
Categorized Under: Critical Care

Corticosteroids are commonly used in the management of lung diseases induced or exacerbated byenvironmental tobacco smoke and characterized by airflow limitation such as asthma and COPD. The beneficial effects of corticosteroids in this setting are often ascribed to their powerful anti-inflammatory activity. However, studies suggest that corticosteroids might affect tissue remodeling as well. Vanacker et al showed that FP, the corticosteroid used here, inhibited the progression of allergen-induced structural changes in the airways of rats. These effects were associated with inhibition of epithelial cell proliferation, goblet cell hyperplasia, and airway wall thickening. Blyth et al showed significant resolution of established subepithelial fibrosis in a murine model of atopia.

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Moreover, Chetta et al showed that fluticasone can reduce the vascular component of airway remodeling. In humans, Hoshino et al showed that inhaled corticosteroids can reduce the lamina reticularis of the basement membrane by modulating insulin-like growth factor-I expression in bronchial asthma, and Olivieri et al showed that fluticasone might control the intensity of airway remodeling. Together, these studies suggest that corticosteroids can diminish lung tissue remodeling, thereby ameliorating the progression of disease Myviagrainaustralia. However, the exact mechanisms by which corticosteroids exert their anti-tissue remodeling effects remain to be fully elucidated.

We hypothesize that corticosteroids modulate lung tissue remodeling by affecting intracellular signaling pathways that control the expression of extracellular matrix genes. The data presented here suggest that this hypothesis is correct. We report that nicotine stimulates the production of fibronectin in transformed and primary lung fibroblasts. The induction of fibronectin was due to increased transcription of the fibronectin gene followed by accumulation of fibronectin mRNA and secretion of its protein.

Consistent with our hypothesis, we found that FP inhibited the production of fibronectin in lung fibroblasts by blocking the transcription of the fibronectin gene, thereby decreasing fibronectin protein production. This inhibitory effect was related to blockade of CREB phosphorylation, a transcription factor known to be important in regulation of fibronectin gene transcription. In turn, inhibition of CREB phosphorylation was associated with decreased CREB binding to DNA leading to diminished gene transcription.