Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

In asthma T cells are characterized by an increased activation state and by reduced apoptosis

Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients

Background: Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms. Methods: The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13). Results: In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter. Conclusions: This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD. © 2012 Pace et al

Role of PGE2 in the invasiveness, growth and protection of cancer cells in malignant pleuritis

Abstract The recurrence of pleural effusions is a common event in a variety of neoplastic diseases. The objective of this study was to identify the mechanisms promoting the homing and growth of cancer cells within the pleural space. A cancer cell line recovered from malignant pleural fluids (lung adenocarcinoma cell line) that constitutively expresses cyclooxygenase 2 (COX-2) and all types of prostaglandin receptors was studied. It was first demonstrated using a matrigel system, that malignant pleural fluids increase the invasiveness of adenocarcinoma cells more than congestive heart failure (CHF) pleural fluids. Moreover, exposure to exudative malignant, but not to CHF pleural fluids, increased the mRNA (measured by real-time polymerase chain reaction (PCR)) and protein expression of COX-2 (measured by Western blot), as well as the activation and nuclear translocation of nuclear factor kappaB (NFkappaB) in cancer cells. These events are all actively regulated by prostaglandin E2 (PGE2), since the addition of synthetic PGE2 to cancer cells and the depletion of PGE2 from malignant pleural fluids or the inhibition of COX-2 activity significantly increased and reduced these phenomena, respectively. Moreover, malignant pleural effusions and synthetic PGE2 increased the long-term proliferation of cancer cells and reverted the impairment in long-term proliferation due to talc exposure. This study demonstrates that PGE2 present in malignant effusions contributes to cancer expansion and may protect cancer cells by anti-proliferative effects induced by talc