Haemophilus influenzae induces steroid-resistant inflammatory responses in COPD
| Autor: | Amanda Iglesias, Alvar Agusti, Andreas Jahn, Borja G. Cosío, Hanaa Shafiek, Xavier Busquets |
|---|---|
| Přispěvatelé: | Universitat de Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
teofilina glucocorticoides Colonization Nuclear Factor-κB medicine.medical_treatment dexametasona humanos Pharmacology broncodilatadores medicine.disease_cause Dexamethasone Haemophilus influenzae Cromatina Pulmonary Disease Chronic Obstructive infecciones del tracto respiratorio macrófagos Respiratory Tract Infections Malalties pulmonars obstructives cròniques mediana edad anciano U937 cell Smoking NF-kappa B línea celular Middle Aged adulto Inflamació Chromatin Bronchodilator Agents Cytokine Cytokines Female medicine.symptom Research Article medicine.drug Pulmonary and Respiratory Medicine Adult Haemophilus Infections Blotting Western estudios de casos y controles Inflammation In Vitro Techniques Histone Deacetylases Cell Line COPD exacerbation Theophylline inflamación Macrophages Alveolar medicine Nuclear Factor-kappa B Humans Histone deacetylase Chronic obstructive pulmonary diseases Glucocorticoides Glucocorticoids Aged histona desacetilasas business.industry Macrophages hábito de fumar NFKB1 Case-Control Studies Immunology infecciones por Haemophilus citocinas business |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona BMC Pulmonary Medicine Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | Background: Chronic 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. Methods: The 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-kappa B) activation in a macrophage-like cell line (PMA-transformed U937 cells) co-cultured with epithelial cells. Experiments were repeated with dexamethasone (1 mu M) and/or the HDAC enhancer theophylline (10 mu M). Results: Haemophilus influenzae induced a steroid-resistant inflammatory response in AM from COPD and controls and decreased HDAC activity, activated NF-kappa B and induced the secretion of several cytokines (IL-6, IL-8, IL-1 beta, IL-10 and TNF-alpha) (p < 0.001 for all comparisons) in the macrophage-like cell line. Dexamethasone reduced NF-kappa B 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-kappa B activation. Conclusions: These results indicate that Haemophilus influenzae reduces HDAC activity and induces a NF-kappa B 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. This project was supported by a grant from the Institute of Health Carlos III (FIS 04/2146), Ciberes and ABEMAR. Authors thank Dr Catalina Crespi for her assistance in the Cytometric Bead Assay, and Dr Antonio Oliver for his generous gift of NTHi strain.; Supported by FIS 04/2146, Ciberes and ABEMAR. |
| Databáze: | OpenAIRE |
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