Publications
255 results found
Donnelly LE, 2005, Resveratrol:: an anti-oxidant or a potent NF-κB inhibitor?, Publisher: BLACKWELL PUBLISHING, Pages: 2-3, ISSN: 0019-2805
Culpitt SV, Rogers DF, Traves SL, et al., 2005, Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma., Respir Med, Vol: 99, Pages: 703-710, ISSN: 0954-6111
Asthma and chronic obstructive pulmonary disease (COPD) are different conditions with contrasting airway inflammation and parenchymal disease patterns. A number of matrix metalloproteases (MMPs) are implicated in the pathophysiology of COPD and asthma. Different profiles of airway MMPs may, therefore, be expected in asthma and COPD. The present study compared MMP profiles in the airways of non-smokers, non-symptomatic cigarette smokers, and patients with COPD or asthma (n = 15 subjects per group). Induced sputum was assessed for MMP-1, -2, -3, -8 and -9, and tissue inhibitor of metalloproteases (TIMP)-1 by ELISA. Gelatinase activity was determined by zymography. Sputum from COPD patients contained increased levels of MMP-1, -8 and -9 compared with the other groups (2-7-fold, depending upon group). MMP-9 activity was elevated in COPD sputum by 3-12-fold above the other groups. Sputum from COPD patients had 3-fold higher levels of TIMP-1 than samples from asthmatics or controls, but was not different to smokers. FEV1 correlated negatively with MMP-1, -8, -9, MMP-9 activity and TIMP-1, whereas percent neutrophils in sputum correlated positively with MMP-1, -8, -9, TIMP-1 and MMP-9 activity. The MMP profile in COPD differs to that in asthma and cigarette smokers. This may contribute to, or be a marker of, different pathophysiologies of asthma and COPD.
Birrell MA, McCluskie K, Wong SS, et al., 2005, Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-κB-independent mechanism, FASEB JOURNAL, Vol: 19, Pages: 840-+, ISSN: 0892-6638
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- Citations: 140
Suzanne L Traves, 2005, Cytokines and Chemokines in Airway Inflammation, New Perspectives in Monitoring Lung Inflammation, Editors: Montuschi, Florida, USA, Publisher: CRC Press, Pages: 183-209, ISBN: 9780415324656
Smith SJ, Cieslinski LB, Newton R, et al., 2004, Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: In vitro studies in human monocytes, lung macrophages, and CD8(+) T-lymphocytes, MOLECULAR PHARMACOLOGY, Vol: 66, Pages: 1679-1689, ISSN: 0026-895X
Donnelly LE, Newton R, Kennedy GE, et al., 2004, Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 287, Pages: L774-L783, ISSN: 1040-0605
Chivers JE, Cambridge LM, Catley MC, et al., 2004, Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E<sub>2</sub> release, EUROPEAN JOURNAL OF BIOCHEMISTRY, Vol: 271, Pages: 4042-4052, ISSN: 0014-2956
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- Citations: 41
Donnelly LE, Barnes PJ, 2004, Acidic mammalian chitinase - a potential target for asthma therapy, TRENDS IN PHARMACOLOGICAL SCIENCES, Vol: 25, Pages: 509-511, ISSN: 0165-6147
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- Citations: 70
Traves SL, Smith SJ, Barnes PJ, et al., 2004, Specific CXC but not CC chemokines cause elevated monocyte migration in COPD:: a role for CXCR<sub>2</sub>, JOURNAL OF LEUKOCYTE BIOLOGY, Vol: 76, Pages: 441-450, ISSN: 0741-5400
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- Citations: 142
Atzori L, Caramori G, Lim S, et al., 2004, Effect of cigarette smoking on haem-oxygenase expression in alveolar macrophages, RESPIRATORY MEDICINE, Vol: 98, Pages: 530-535, ISSN: 0954-6111
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- Citations: 8
Horváth I, Donnelly LE, Kiss A, et al., 2004, Exhaled nitric oxide and hydrogen peroxide concentrations in asthmatic smokers, RESPIRATION, Vol: 71, Pages: 463-468, ISSN: 0025-7931
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- Citations: 63
Culpitt SV, Rogers DF, Fenwick PS, et al., 2003, Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD., Thorax, Vol: 58, Pages: 942-946, ISSN: 0040-6376
The pathophysiology of chronic obstructive pulmonary disease (COPD) features pulmonary inflammation with a predominant alveolar macrophage involvement. Bronchoalveolar macrophages from patients with COPD release increased amounts of inflammatory cytokines in vitro, an effect that is not inhibited by the glucocorticosteroid dexamethasone. Resveratrol (3,5,4'-trihydroxystilbene) is a component of red wine extract that has anti-inflammatory and antioxidant properties. A study was undertaken to determine whether or not resveratrol would inhibit cytokine release in vitro by alveolar macrophages from patients with COPD.
Csoma Z, Bush A, Wilson NM, et al., 2003, Nitric oxide metabolites are not reduced in exhaled breath condensate of patients with primary ciliary dyskinesia, CHEST, Vol: 124, Pages: 633-638, ISSN: 0012-3692
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- Citations: 39
Nabeyrat E, Jones GE, Fenwick PS, et al., 2003, Mitogen-activated protein kinases mediate peroxynitrite-induced cell death in human bronchial epithelial cells, American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol: 284, ISSN: 1040-0605
Peroxynitrite, formed by the reaction of nitric oxide (NO·) with superoxide anions (O2-·), may play a role in the pathophysiology of inflammation. The effects of 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, on the human bronchial epithelial cell line BEAS-2B, were examined. SIN-1 exposure resulted in cell death in a time- and dose-dependent manner. Depletion of intracellular glutathione increased the vulnerability of the cells. Pretreatment with Mn(III)tetrakis(Nmethyl-4′-pyridyl)porphyrin (MnTMPyP) or hydroxocobalamin (HC), O2-· and NO· scavengers, respectively, reduced significantly SIN-1-induced cell death (18.66 ± 3.57 vs. 77.01 ± 14.07 or 82.20 ± 9.64, % cell viability SIN-1 vs. MnTMPyP or HC). Moreover, the mitogen-activated protein kinases (MAPK) p44/42 (ERK), p38, and p54/46 (JNK) were also activated in a time- and concentration-dependent manner. PD-98059 and SB-239063, specific inhibitors of ERK and p38 MAPK pathways, failed to protect cells against 1 mM SIN-1. However, PD-98059 partially inhibited (60% cell survival) SIN-1 effects at ≤0.25 mM, and this was increased with the inclusion of SB-239063. Therefore, MAPKs may mediate signal transduction pathways induced by peroxynitrite in lung epithelial cells leading to cell death.
Nabeyrat E, Jones GE, Fenwick PS, et al., 2003, Mitogen-activated protein kinases mediate peroxynitrite-induced cell death in human bronchial epithelial cells., Am J Physiol Lung Cell Mol Physiol, Vol: 284, Pages: L1112-L1120, ISSN: 1040-0605
Peroxynitrite, formed by the reaction of nitric oxide (NO. ) with superoxide anions (O(2)(-).), may play a role in the pathophysiology of inflammation. The effects of 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, on the human bronchial epithelial cell line BEAS-2B, were examined. SIN-1 exposure resulted in cell death in a time- and dose-dependent manner. Depletion of intracellular glutathione increased the vulnerability of the cells. Pretreatment with Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP) or hydroxocobalamin (HC), O(2)(-). and NO. scavengers, respectively, reduced significantly SIN-1-induced cell death (18.66 +/- 3.57 vs. 77.01 +/- 14.07 or 82.20 +/- 9.64, % cell viability SIN-1 vs. MnTMPyP or HC). Moreover, the mitogen-activated protein kinases (MAPK) p44/42 (ERK), p38, and p54/46 (JNK) were also activated in a time- and concentration-dependent manner. PD-98059 and SB-239063, specific inhibitors of ERK and p38 MAPK pathways, failed to protect cells against 1 mM SIN-1. However, PD-98059 partially inhibited (60% cell survival) SIN-1 effects at < or =0.25 mM, and this was increased with the inclusion of SB-239063. Therefore, MAPKs may mediate signal transduction pathways induced by peroxynitrite in lung epithelial cells leading to cell death.
Hansel TT, Kharitonov SA, Donnelly LE, et al., 2003, A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics, FASEB JOURNAL, Vol: 17, Pages: 1298-+, ISSN: 0892-6638
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- Citations: 158
Smith SJ, Brookes-Fazakerley S, Donnelly LE, et al., 2003, Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells, American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol: 284, ISSN: 1040-0605
We have determined the expression of phosphodiesterase (PDE) 7A1 and PDE7A2 in human cells that have been implicated in the pathogenesis of chronic obstructive pulmonary disease and asthma. Messenger RNA transcripts were detected by RT-PCR in T lymphocytes, monocytes, neutrophils, airway and vascular smooth muscle cells, lung fibroblasts, epithelial cells, and cardiac myocytes. Human epithelial, T cell, eosinophil, and lung fibroblast cell lines were also positive for PDE7A1 and PDE7A2 mRNA transcripts. By Western immunoblot analyses the amount of PDE7A1 was greatest in T cell lines, peripheral blood T lymphocytes, epithelial cell lines, airway and vascular smooth muscle cells, lung fibroblasts, and eosinophils but was not detected in neutrophils. In contrast, PDE7A2 protein, which was identified in human cardiac myocytes, was not found in any of the other cell types investigated. Immunoconfocal analyses showed that PDE7A was expressed in neutrophils and alveolar macrophages. As the expression of PDE7A mirrors the distribution of PDE4 we speculate that this enzyme could be a target for novel anti-inflammatory drugs.
Smith SJ, Brookes-Fazakerley S, Donnelly LE, et al., 2003, Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 284, Pages: L279-L289, ISSN: 1040-0605
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- Citations: 102
Hansel TT, Kharitonov SA, Donnelly LE, et al., 2003, A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics., The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol: 17, Pages: 1298-1300
The inducible isoenzyme of nitric oxide synthase (iNOS) generates nitric oxide (NO) in inflammatory diseases such as asthma. The prodrug L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted in vivo to the active metabolite L-N6-(1-iminoethyl)lysine (L-NIL). Initially, we performed in vitro experiments in human primary airway epithelial cells to demonstrate that L-NIL causes inhibition of iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered as a single oral dose (20 or 200 mg) in separate cohorts of healthy volunteers (two groups of n=12) and mild asthmatic patients (two groups of n=12). SC-51 (200 mg) reduced exhaled breath NO levels to <2 ppb in both healthy volunteers (P<0.001) and mild asthmatics (P<0.001) within 15 min, representing >90% inhibition of baseline levels of NO in asthmatic patients, with the effects lasting at least 72 h. There were no significant effects on blood pressure, pulse rate, or respiratory function (FEV1). This study demonstrates that an inhibitor of iNOS produces marked inhibition of exhaled breath NO in normal and asthmatic subjects without producing the side effects observed following the systemic administration of non-selective NOS inhibitors, and thus provides support for the potential use of iNOS inhibitors to treat a range of inflammatory clinical disorders.
Culpitt SV, Rogers DF, Shah P, et al., 2003, Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 167, Pages: 24-31, ISSN: 1073-449X
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- Citations: 227
Donnelly LE, Rogers DF, 2003, Antiproteases and retinoids for treatment of chronic obstructive pulmonary disease, Exp Opinion Therapeutic Drugs, Vol: 13, Pages: 1345-1372, ISSN: 1354-3776
Donnelly LE, Rogers DF, 2003, Therapy for chronic obstructive pulmonary disease in the 21st century, DRUGS, Vol: 63, Pages: 1973-1998, ISSN: 0012-6667
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- Citations: 66
Eynott PR, Groneberg DA, Caramori G, et al., 2002, Role of nitric oxide in allergic inflammation and bronchial hyperresponsiveness (vol 452, pg 123, 2002), EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 455, Pages: 79-79, ISSN: 0014-2999
Russell REK, Thorley A, Culpitt SV, et al., 2002, Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 283, Pages: L867-L873, ISSN: 1040-0605
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- Citations: 187
Kharitonov SA, Donnelly LE, Montuschi P, et al., 2002, Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma, THORAX, Vol: 57, Pages: 889-896, ISSN: 0040-6376
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- Citations: 181
Russell RE, Thorley A, Culpitt SV, et al., 2002, Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases, Am J Physiol Lung Cell Mol Physiol, Vol: 283, Pages: L867-73
Eynott PR, Groneberg DA, Caramori G, et al., 2002, Role of nitric oxide in allergic inflammation and bronchial hyperresponsiveness, EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 452, Pages: 123-133, ISSN: 0014-2999
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- Citations: 61
Traves SL, Culpitt SV, Russell REK, et al., 2002, Increased levels of the chemokines GROα and MCP-1 in sputum samples from patients with COPD, THORAX, Vol: 57, Pages: 590-595, ISSN: 0040-6376
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- Citations: 264
Culpitt SV, de Matos C, Russell RE, et al., 2002, Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 165, Pages: 1371-1376, ISSN: 1073-449X
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- Citations: 129
Russell REK, Culpitt SV, DeMatos C, et al., 2002, Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 26, Pages: 602-609, ISSN: 1044-1549
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- Citations: 320
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