Cilomilast counteracts the effects of cigarette smoke in airway epithelial cells
- Authors: Pace, E; Ferraro, M; Uasuf, C; Giarratano, A; La Grutta, S; Liotta, G; Johnson, M; Gjomarkaj, M
- Publication year: 2011
- Type: Articolo in rivista (Articolo in rivista)
- Key words: Respiratory Mucosa; Tobacco Use Disorder; Humans; Lymphocytes; Chemotaxis; Toll-Like Receptor 4; Smoke; Nitriles; Cyclohexanecarboxylic Acids; Gene Expression Regulation; Phosphodiesterase 4 Inhibitors; Interleukin-8; Chemokine CXCL10; Cell Line; Signal Transduction
- OA Link: http://hdl.handle.net/10447/105635
Abstract
Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Cilomilast, a phosphodiesterase-4 inhibitor, inhibits cigarette smoke-induced neutrophilia. This study was aimed to explore whether cilomilast, in a human bronchial epithelial cell line (16-HBE), counteracted CSE effects. In particular, TLR4 expression, IP-10 and IL-8 release, lymphocyte and neutrophil chemotactic activity and ERK and IkBa phosphorylation in CSE and LPS-stimulated 16-HBE were assessed. CSE increased TLR4 expression, reduced IP-10 release and lymphocyte chemotactic activity and increased IL-8 release and neutrophil chemotactic activity. Cilomilast reduced TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. All these cilomilast mediated effects were associated with a reduced ERK1/2 and with an increased IkBa phosphorylation. In conclusion, the present study provides compelling evidences that cilomilast may be considered a possible valid therapeutic option in controlling inflammatory processes present in smokers.