Abstract
The tobacco smoking habit interferes with the innate host defence system against infections. Recurrent infections in COPD patients concur to disease progression and accelerate functional respiratory decline. The general aims of the present study were to assess the effects of ceftaroline (CEFT) on innate immunity receptors (TLR2 and TLR4) and on pro-inflammatory responses in airway epithelial cells (16HBE) as well as in immunocompetent cells (THP1) +/- cigarette smoke extracts (CSE 10%) and in some experiments +/- IL1β.
Cell tolerability was tested by MTS and by annexin V binding method. TLR2, TLR4 and LPS binding were assessed by flow cytometry. IL-8 was assessed by Real Time PCR.
Among the different tested concentrations of CEFT, CEFT 10-7M was well tolerated and then selected for the subsequent experiments in 16HBE and THP1 cell lines. CSE induced TLR4 and TLR2 expression in both cell lines and CEFT was able to counteract the CSE effect on TLR2 expression in 16HBE but not in THP1. Differently, CEFT was able to counteract the CSE effect on TLR4 expression in THP1 but not in16HBE. CEFT was able to reduce LPS binding in both cell lines exposed to CSE. CEFT was able to reduce IL-8 in cells stimulated with both CSE and IL-1β.
In conclusion, CEFT is able to counteract the effects of CSE on the innate immunity and pro-inflammatory responses modulating TLR2 and TLR4 expression and IL-8 production.
Funded by Astra-Zeneca.
- Copyright ©ERS 2015