Cilomilast counteracts the effects of cigarette smoke in airway epithelial cells.

2010

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 expressi…

Innate Immunity Responses Are Differently Altered in Central and Distal Airways of COPD Patients.

2009

Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells.

2008

Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Toll-like receptor (TLR) expression and activation in a human bronchial epithelial cell line (16-HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor-kappaB (NF-kappaB) activation, the release of interleukin-8 (IL-8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced bot…

TLR4 upregulation underpins airway neutrophilia in smokers with chronic obstructive pulmonary disease and acute respiratory failure

2010

Activation of Toll-like receptors (TLR) seems to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Upon TLR activation the release of defensins, including human beta defensin 2 (HBD-2), may occur. In this study, we explored the innate responses in patients with respiratory failure, with and without COPD, requiring intubation and mechanical ventilation. Mini-bronchoalveolar lavage (mini-BAL) samples were collected from nonsmoker subjects without COPD (n = 10), smokers without COPD (n = 6), and smokers with COPD (n = 15). TLR4, TLR2, and HBD-2 expression was evaluated by immunocytochemistry; interleukin (IL)-8, IP-10, and HBD-2 concentrations were evaluated by e…