Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.


METHODS
The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry. To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFalpha and IL-6 secreted were determined by ELISA.


RESULTS
We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function. Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers. In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either. At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients. This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner. Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers.


CONCLUSIONS
Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients.
Pons
Jaume
J
Unidad de Investigación, Hospital Son Dureta, Institut Universitari d'Investigacions en Ciències de la Salut, Palma Mallorca, Spain. jpons@hsd.es
Sauleda
Jaume
J
Regueiro
Verónica
V
Santos
Carmen
C
López
Meritxell
M
Ferrer
Joana
J
Agustí
Alvar G N
AG
Bengoechea
José A
JA
D000368:Aged; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation / Q000502:physiology*
D051195:Toll-Like Receptor 2