Haemophilus influenzae induces steroid-resistant inflammatory responses in COPDReport as inadecuate




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BMC Pulmonary Medicine

, 15:157

COPD and occupational lung disease

Abstract

BackgroundChronic obstructive pulmonary disease COPD is an inflammatory disorder partially resistant to glucocorticoids. A reduced histone deacetylase HDAC activity has been proposed to explain this resistance. Haemophilus influenzae frequently colonizes the airways of COPD patients, where it enhances inflammation. The effects of Haemophilus influenzae on HDAC activity have not been investigated before.

MethodsThe effects of the presence or absence of Haemophilus influenzae ex-vivo and in vitro were studied. To this end, we determined: 1 cytokine release in alveolar macrophages AM from 7 patients with COPD, 5 healthy smokers, 6 healthy non-smokers and 2 HDAC activity, nuclear factor kappa B NF-κB activation in a macrophage-like cell line PMA-transformed U937 cells co-cultured with epithelial cells. Experiments were repeated with dexamethasone 1 μM and-or the HDAC enhancer theophylline 10 μM.

ResultsHaemophilus influenzae induced a steroid-resistant inflammatory response in AM from COPD and controls and decreased HDAC activity, activated NF-κB and induced the secretion of several cytokines IL-6, IL-8, IL-1β, IL-10 and TNF-α p < 0.001 for all comparisons in the macrophage-like cell line. Dexamethasone reduced NF-κB activation but it did not modify HDAC activity. The addition of theophylline to dexamethasone increased HDAC activity and suppressed cytokine release completely, without modifying NF-κB activation.

ConclusionsThese results indicate that Haemophilus influenzae reduces HDAC activity and induces a NF-κB mediated inflammatory response that is only partially suppressed by glucocorticoids irrespective of having COPD. Yet, the latter can be fully restored by targeting HDAC activity.

KeywordsCOPD exacerbation Glucocorticoids Colonization Histone deacetylase Nuclear Factor-κB Theophylline AbbreviationsCOPDChronic obstructive pulmonary disease

HDACHistone deacetylase

AMAlveolar macrophages

NF-κBNuclear factor kappa B

GRGlucocorticoid receptor

BALBronchoalveolar lavage

FCSFetal calf serum

ICAM-1Intercellular adhesion molecule 1

ILInterleukin

TNFTumor necrosis factor

Electronic supplementary materialThe online version of this article doi:10.1186-s12890-015-0155-3 contains supplementary material, which is available to authorized users.

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Author: Borja G. Cosío - Andreas Jahn - Amanda Iglesias - Hanaa Shafiek - Xavier Busquets - Alvar Agustí

Source: https://link.springer.com/article/10.1186/s12890-015-0155-3







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