Anti-fibrotic Effects of ONO-EF-345, a Specific Phosphodiesterase IV inhibitor, on Lung Fibroblasts

Abstract

Phosphodiesterase (PDE) IV inhibitors have been shown to inhibit various inflammatory reactions in pulmonary diseases such as bronchial asthma and chronic obstructive lung diseases (COPD). However, there have been no studies evaluating the effect of PDE IV inhibitors on airway fibrosis, which is a critical feature of airway remodeling in asthma and COPD. We therefore examined whether ONO-EF-345 (ONO), a PDE IV inhibitor, affected the function of lung fibroblasts. ONO suppressed TGF-ß-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited TGF-ß-induced a- smooth muscle actin (SMA) protein expression. ONO did not affect Smad2 phosphorylation or Smad7 expression. However, ONO reduced JNK and p38 activation, which regulates TGF-ß-induced COL1 expression. These results indicate that PDE IV inhibitors exert anti-fibrotic effects through the JNK and/or p38 pathways.