An Inhibitor of Nuclear Factor-Kappa B Pathway Attenuates the Release of TGF-β1 and Inhibits the Fibrogenic Progress in a Model of Airway Remodeling Induced by Acrolein.

Abstract

Airway inflammation, airway hypersecretion, and airway remodeling are believed to be involved in the process of lung fibrosis. Nowadays, acrolein is widely used to establish the model of airway remodeling. An active component of propolis, named caffeic acid phenethyl ester (CAPE), is recognized as an inhibitor of the NF-κB pathway and shows anti-inflammatory effect. The purpose of this study was to investigate the protective effect of CAPE on acrolein-induced airway remodeling. 24 mice were divided into 4 groups: control group; acrolein group, mice received acrolein (inhalation of acrolein for 20 days); CAPE group, mice received CAPE (30 mg/kg); and acrolein+CAPE group, mice received acrolein and CAPE. After 20 days, lung tissue was removed for histopathology and immunohistochemical evaluations. TGF-β1 and Muc5ac levels were measured at the protein and molecular levels. Additionally, the phospho-P65/P65 values in the airway smooth muscle cells treated with TGF-β1 or CAPE were detected by Western blot. The results showed that compared with the control, subepithelial collagen deposition, airway inflammation, and peribronchus fibrosis were inhibited in the group treated with CAPE. Furthermore, TGF-β1 was significantly decreased in the acrolein+CAPE group compared with the acrolein group. Additionally, we identified CAPE inhibited P65 phosphorylation. However, CAPE did not inhibit the Muc5ac overproduction and hypersecretion induced by acrolein. In conclusion, as an inhibitor of the NF-κB pathway, CAPE attenuated the release of TGF-β1, which inhibited the fibrogenic progress induced by acrolein in mice and took no effect on inhibiting airway mucus hypersecretion.