Anti‐fibrotic effect of ciglitazone in HRV‐induced airway remodelling cell model.

Fibrosis is an important phenomenon as it can occur early in the pathogenesis of asthma; it may be associated with disease severity and resistance to therapy. There is a strong evidence that infection caused by human rhinovirus (HRV) contributes to remodelling process, but there is lack of studies clearly explaining this pathway. Synthetic peroxisome proliferator‐activated receptor (PPAR) γ presents immunomodulatory and anti‐inflammatory features. In this study, we examined immunomodulatory properties of ciglitazone – PPAR‐γ agonist, in development and modulation of airway remodelling. Epithelial cells (NHBE) and two lines of fibroblasts (WI‐38, HFL1) were stimulated with ciglitazone and rhinovirus. The expression of genes related to airway remodelling process were analysed in the cells; moreover NF‐κB, c‐Myc and STAT3 were silenced in order to estimate potential pathways involved. Ciglitazone decreased mRNA expression of MMP‐9 and TGF‐β. It also modified the expression of α‐SMA and collagen after rhinovirus infection. Transcription factors knockdown altered the levels of expression. The results suggest possible anti‐fibrotic activity of PPAR‐γ agonist in human airway cells. Ciglitazone has been shown to be dependent on NF‐κB‐ and STAT3‐related pathways, thus, the PPAR‐γ agonist may have therapeutic potential for the treatment of airway remodelling in asthma. [ABSTRACT FROM AUTHOR]