Abstract | BACKGROUND: METHOD: RESULTS:
Dexamethasone significantly inhibited NTHi induced TNF-α, IL-6 and IL-10 from COPD macrophages but, CXCL8 was not suppressed. BIRB-796 combined with dexamethasone caused significantly greater inhibition of all cytokines than either drug alone (p < 0.05 all comparisons). NTHi caused phosphorylation of GR S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK. NTHi altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206, CD163 and HLA-DR. CONCLUSION: NTHi exposure causes p38 MAPK dependent GR phosphorylation associated with decreased GR function in COPD alveolar macrophages. Combining a p38 MAPK inhibitor with corticosteroids can enhance anti-inflammatory effects during NTHi exposure of COPD alveolar macrophages. NTHi causes macrophage polarisation that favours bacterial persistence.
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Authors | Rana M Khalaf, Simon R Lea, Hannah J Metcalfe, Dave Singh |
Journal | Respiratory research
(Respir Res)
Vol. 18
Issue 1
Pg. 61
(04 18 2017)
ISSN: 1465-993X [Electronic] England |
PMID | 28420398
(Publication Type: Journal Article)
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Chemical References |
- Adrenal Cortex Hormones
- Cytokines
- Naphthalenes
- Pyrazoles
- Dexamethasone
- doramapimod
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Topics |
- Adrenal Cortex Hormones
(administration & dosage)
- Aged
- Cells, Cultured
- Cytokines
(immunology)
- Dexamethasone
(administration & dosage)
- Dose-Response Relationship, Drug
- Drug Resistance
(immunology)
- Haemophilus Infections
(drug therapy, immunology)
- Humans
- Macrophages
(drug effects, immunology)
- Naphthalenes
(administration & dosage)
- Pulmonary Alveoli
(drug effects, immunology, pathology)
- Pulmonary Disease, Chronic Obstructive
(drug therapy, immunology, pathology)
- Pyrazoles
(administration & dosage)
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