Publications
256 results found
Heward JA, Ilott NE, Roux B, et al., 2014, Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes, Publisher: WILEY-BLACKWELL, Pages: 110-110, ISSN: 0019-2805
Day AMW, Barnes PJ, Donnelly LE, 2014, Lack of plasticity in macrophages from chronic obstructive pulmonary disease (COPD) patients, Publisher: WILEY-BLACKWELL, Pages: 150-150, ISSN: 0019-2805
Donnelly LE, Singh R, Mackay AJ, et al., 2014, Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease, Respiratory Research, Vol: 15, ISSN: 1465-993X
Donnelly LE, 2014, The Lipidome: A New Player in Chronic Obstructive Pulmonary Disease Pathophysiology?, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 190, Pages: 124-125, ISSN: 1073-449X
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- Citations: 3
Liang Z, Zhang Q, Thomas CMR, et al., 2014, Impaired macrophage phagocytosis of bacteria in severe asthma, RESPIRATORY RESEARCH, Vol: 15
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- Citations: 74
Iiott NE, Heward JA, Roux B, et al., 2014, Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes, Nature Communications, Vol: 5, Pages: 1-14, ISSN: 2041-1723
Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown of nuclear-localized, NF-κB-regulated, eRNAs (IL1β-eRNA) and RBT (IL1β-RBT46) surrounding the IL1β locus, attenuates LPS-induced messenger RNA transcription and release of the proinflammatory mediators, IL1β and CXCL8. We predict that lncRNAs can be important regulators of the human innate immune response.
Forbes B, O'Lone R, Allen PP, et al., 2014, Challenges for inhaled drug discovery and development: Induced alveolar macrophage responses, ADVANCED DRUG DELIVERY REVIEWS, Vol: 71, Pages: 15-33, ISSN: 0169-409X
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- Citations: 60
Bewley M, Budd R, Singh D, et al., 2014, Alveolar Macrophages During COPD Demonstrate Reduced Apoptosis-Associated Bacterial Killing And Reduced Mitochondrial Reactive Oxygen Species-Dependent Killing, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X
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- Citations: 1
Singh R, Such K, Kowlessar BS, et al., 2013, MACROPHAGE PHAGOCYTOSIS IN COPD PATIENTS AT EXACERBATION COMPARED TO STABLE STATE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A159-A159, ISSN: 0040-6376
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- Citations: 1
Chana KK, Fenwick PS, Nicholson AG, et al., 2013, Identiļ¬cation of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749
BackgroundIn patients with chronic obstructive pulmonary disease (COPD), pulmonary macrophages increase in number, release increased levels of inflammatory mediators, and respond poorly to glucocorticosteroids. Whether this is due to a change in macrophage phenotype or localized activation is unknown.ObjectiveWe sought to investigate whether macrophages from patients with COPD are a distinct phenotype.MethodsMacrophage populations were isolated from human lung tissue from nonsmokers, smokers, and patients with COPD by using Percoll density gradients. Five macrophage populations were isolated on the basis of density (1.011-1.023, 1.023-1.036, 1.036-1.048, 1.048-1.061, and 1.061-1.073 g/mL), and cell-surface expression of CD14, CD16, CD163, CD40, and CD206 was assessed by using flow cytometry. Release of active matrix metalloproteinase 9, TNF-α, CXCL8, and IL-10 was measured by using ELISA.ResultsThe 2 least dense fractions were more than 90% apoptotic/necrotic, with the remaining fractions greater than 70% viable. Macrophages from nonsmokers and smokers were CD163+, CD206+, CD14+, and CD40−, whereas macrophages from patients with COPD were less defined, showing significantly lower expression of all receptors. There were no differences in receptor expression associated with density. Macrophages from patients with COPD of a density of 1.036 to 1.048 g/mL released higher levels of active matrix metalloproteinase 9 compared with cells from nonsmokers, with no difference between the remaining fractions. This population of macrophages from patients with COPD was less responsive to budesonide compared with those from nonsmokers and smokers when stimulated with LPS. Glucocorticosteroid insensitivity was selective for proinflammatory cytokines because budesonide inhibition of LPS-stimulated IL-10 release was similar for all macrophages.ConclusionsThis study identifies a specific macrophage phenotype in the lungs of patients with COPD who are glucocorticosteroid in
Day AMW, Barnes PJ, Donnelly LE, 2013, COPD Monocytes Differentiate into Pro-inflammatory Macrophages Regardless of Environment, European Respiratory Society Annual Congress, Publisher: European Respiratory Journal
Fenwick P, Rao V, Kilty I, et al., 2013, Inhibition of IRAK4 suppresses chemokine release from human bronchial epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Sehra G, Barnes P, Rogers D, et al., 2013, Effect of diesel exhaust particles (DEP) on monocyte-derived macrophage (MDM) mediator release and phagocytosis in chronic obstructive pulmonary disease (COPD), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Singh R, Chana K, Such K, et al., 2013, Relationship between monocyte-derived macrophage phagocytosis and airway inflammation in stable COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Bewley M, Chana K, Budd R, et al., 2013, Inhibition of p38 mitogen-activated protein kinase has no effect on macrophage phagocytosis of bacteria in patients with COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Such K, Singh R, Wedzicha J, et al., 2013, Increased susceptibility of M2 monocyte-derived macrophages from COPD patients to oxidative stress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Guney TG, Holloway R, Taylor A, et al., 2013, Increased expression of sphingosine-1-phosphate and S1PR2 are associated with attenuated macrophage phagocytosis in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Holloway R, Nicholson G, Leaker B, et al., 2013, Detection of STAT1 phosphorylation in COPD sputum by flow cytometry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Singh R, Mackay A, Patel A, et al., 2013, Concordance between airway inflammation and health status in COPD patients with bacterial colonisation, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Rhodes J, Kilty I, Barnes P, et al., 2013, Effect of JQ-1 on monocyte-derived macrophage (MDM) phagocytosis of bacteria and cytokine release, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Singh R, Patel A, Mackay A, et al., 2013, The species-specific inflammatory response of colonising bacteria in stable COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Day AMW, Barnes PJ, Donnelly LE, 2013, COPD Monocytes Differentiate into Pro-inflammatory Macrophages Irrespective of Their Environment, BALR Summer Conference
Holloway RA, Donnelly LE, 2013, Immunopathogenesis of chronic obstructive pulmonary disease, CURRENT OPINION IN PULMONARY MEDICINE, Vol: 19, Pages: 95-102, ISSN: 1070-5287
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- Citations: 50
Brown SM, Koarai A, Sturton RG, et al., 2013, A role for M<sub>2</sub> and M<sub>3</sub> muscarinic receptors in the contraction of rat and human small airways, EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 702, Pages: 109-115, ISSN: 0014-2999
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- Citations: 27
Singh R, Chana KK, Wright LL, et al., 2012, ASSOCIATION OF DEFECTIVE MONOCYTE-DERIVED MACROPHAGE PHAGOCYTOSIS WITH CLINICAL PHENOTYPES IN STABLE COPD, Winter Meeting of the British-Thoracic-Society 2012, Publisher: BMJ PUBLISHING GROUP, Pages: A175-A176, ISSN: 0040-6376
Macedo P, Rhodes J, Kilty I, et al., 2012, p38 MAPK inhibitors in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Chana KK, Day AM, Ward AJN, et al., 2012, Lack of macrophage plasticity in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Holloway R, Fenwick P, Kilty I, et al., 2012, Defective macrophage phagocytosis in COPD is associated with reduced STAT1 phosphorylation, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Thomas C, Barnes P, Donnelly L, 2012, Reduced phagocytosis of pathogenic bacteria by neutrophils from COPD patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Madge NJ, Donnelly LE, Rogers DF, 2012, Effect of neutrophil supernatants on ex vivo small airway contractility in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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