Publications
212 results found
Tetley TD, 2002, Smoking and the Lung., Drink, Drugs and Dependency. From science to clinical practice., Editors: Caan, De, New York; London, Publisher: Gordon & Breach, Pages: 93-106, ISBN: 9780415278911
Pardo OE, Arcaro A, Salerno G, et al., 2001, Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells, Oncogene, Vol: 20, Pages: 7658-7667, ISSN: 0950-9232
Here, we show that fibroblast growth factor-2 (FGF-2) induces proliferation of H-510 and H-69 small cell lung cancer (SCLC) cells. However, the optimal response to FGF-2 was obtained at 10-fold lower concentrations in H-510 cells. This correlated with the selective activation of the mitogen-activated protein kinase kinase (MEK) pathway in H-510, but not H-69 cells. Moreover, inhibition of MEK with PD098059 blocked FGF-2-induced proliferation in H-510 cells only. Similarly, ribosomal protein S6 kinase 2 (S6K2), a recently identified homologue of S6K1 was activated by FGF-2 in H-510, but not H-69 cells. This activation was independent of phosphatidylinositol-3 kinase, but was sensitive to inhibition of the MEK pathway. These data suggest that S6K2 is a novel downstream target of MEK. The potency of FGF-2 in H-510 cells might reflect this additional MEK/S6K2 signalling. In contrast to S6K2, S6K1 was activated in both SCLC cell lines. Inhibition of the mammalian target of rapamycin with 10 ng/ml rapamycin blocked S6K1 activation and proliferation of both lines. However, even at 100 ng/ml, rapamycin only partially inhibited S6K2. Strikingly, this correlated with inhibition of MEK signalling. Our data indicate that S6K1, and possibly S6K2, are involved in FGF-2-induced SCLC cell growth, a notion supported by the overexpression and higher baseline activity of both isoforms in SCLC lines, as compared to normal human type-II pneumocytes.
Pardo OE, Arcaro A, Salerno G, et al., 2001, Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells, ONCOGENE, Vol: 20, Pages: 7658-7667, ISSN: 0950-9232
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- Citations: 64
Bingle L, Tetley TD, Bingle CD, 2001, Cytokine-mediated induction of the human elafin gene in pulmonary epithelial cells is regulated by nuclear factor-κB, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 25, Pages: 84-91, ISSN: 1044-1549
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- Citations: 53
Witherden IR, Tetley TD, 2001, Isolation and Culture of Human Alveolar Type II Pneumocytes, Human Airway Inflammation: Sampling Techniques and Analytical Protocols, Editors: Rogers, Donnelly, New Jersey, Publisher: Humana Press, Pages: 137-146, ISBN: 9780896039230
Kendall M, Hutton BM, Tetley T, et al., 2001, Investigation of fine atmospheric particle surfaces and lung lining fluid interactions using XPS, Applied Surface Science, Vol: 178, Pages: 27-36
Tetley TD, 2000, Neutrophil- and macrophage-derived proteases in chronic obstructive pulmonary disease and acute respiratory distress syndrome., Acute Lung Injury: From Inflammation to Repair, Editors: Bellingan, Laurent, Amsterdam, Publisher: IOS Press, Pages: 129-142, ISBN: 9789051995039
Mistry R, Snashall PD, Totty N, et al., 1999, Purification and N-terminal amino acid sequence of sheep neutrophil cathepsin G and elastase, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, Vol: 368, Pages: 7-13, ISSN: 0003-9861
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- Citations: 2
Kamal AM, Tetley TD, Corrigan CJ, et al., 1999, Relationship between annexin-1 and secretory leucocyte protease inhibitor (SLPI) in healthy human lungs., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A111-A111, ISSN: 1073-449X
Hall SE, Lim S, Witherden IR, et al., 1999, Lung type II cell and macrophage annexin I release: Differential effects of two glucocorticoids, American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol: 276, ISSN: 1040-0605
Annexin I (lipocortin 1) is abundant in lung secretions. Concentrations rise after oral glucocorticoid, but the effect of inhaled budesonide on annexin I release is unknown. Extracellular annexin I in bronchoalveolar lavage fluid (BALF) from 11 asthmatic patients was unaffected by inhaled budesonide (800 μg twice daily for 4 wk; mean after budesonide, 110 ng/mg albumin; after placebo, 107 ng/mg albumin). Rat alveolar macrophages (AMs) and alveolar epithelial type II (ATII) cells were cultured alone and with budesonide or dexamethasone. Mean basal concentrations of cellular (3.5 rig/106 AMs; 4.4 ng/106 ATII cells) and secreted (1.4 ng/106 AMs; 1.8 ng/106 ATII cells) annexin I were similar in AMs and ATII cells. Although budesonide subdued annexin I secretion from both cell types, dexamethasone stimulated annexin I release. Annexin I release from ATII cells peaked at 10-7 M dexamethasone but at 10-3 M dexamethasone from AMs. Thus, at low concentrations of dexamethasone, ATII cells probably contribute more annexin I to respiratory tract secretions than AMs, although at high concentrations, both cells probably contribute. The study demonstrates previously undescribed differences between glucocorticoids and between AMs and ATII cells with respect to annexin I regulation.
Hall SE, Lim S, Witherden IR, et al., 1999, Lung type II cell and macrophage annexin I release: differential effects of two glucocorticoids, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 276, Pages: L114-L121, ISSN: 1040-0605
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- Citations: 22
Kamal AM, Tetley TD, Witherden IR, et al., 1998, Reduction of nitric oxide release from alveolar macrophages by a lipocortin peptide, MEDIATORS OF INFLAMMATION, Vol: 7, Pages: 93-98, ISSN: 0962-9351
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- Citations: 1
Bingle L, Richards RJ, Fox B, et al., 1997, Susceptibility of lung epithelium to neutrophil elastase: protection by native inhibitors, Mediators of Inflammation, Vol: 6, Pages: 345-354, ISSN: 1466-1861
The development of emphysema is thought to be due to an imbalance of proteases (especially neutrophil elastase [NE]) and antiproteases with loosening of the respiratory epithelium as an early event. We investigated the effect of NE on respiratory epithelial cell adherence in vitro , in the presence of varying concentrations and combinations of native inhibitors, α-1-proteinase inhibitor (PI) and secretory leukoprotease inhibitor (SLPI). SLPI was two to 12 times more effective than PI at preventing the effects of NE, especially when enzyme:inhibitor ratios were almost equivalent. Even when the concentration of SLPI was only 10% of the total (as in normal peripheral lung secretions), it gave greater protection than PI alone. This suggests that SLPI plays an important role in controlling neutrophil elastaseinduced inflammation and tissue damage.
Mistry R, Snashall PD, Totty N, et al., 1997, Purification and characterization of a novel Kazal-type serine proteinase inhibitor of neutrophil elastase from sheep lung, BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, Vol: 1342, Pages: 51-61, ISSN: 0167-4838
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- Citations: 4
Tetley TD, 1997, Matrix metalloproteinases: A role in emphysema?, THORAX, Vol: 52, Pages: 495-495, ISSN: 0040-6376
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- Citations: 10
Mudway IS, Tetley TD, Charalambous K, et al., 1997, Ozone-exposed respiratory tract lining fluid-mediated toxicity in lung macrophages and epithelial type II cells, ISSN: 0954-6111
, 1997, Nitrogen dioxide depletes uric acid and ascorbic acid but not glutathione from lung lining fluid, Vol: 325 ( Pt 1), Pages: 95-99, ISSN: 0264-6021
Smith SF, Roberts NA, Guz A, et al., 1996, Compromised inhibition of human lung lavage cell elastases, FEBS LETTERS, Vol: 390, Pages: 187-190, ISSN: 0014-5793
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- Citations: 6
Tetley TD, Rogers DF, 1996, Development of new treatments for lung disease, Pages: 5-23, ISSN: 0954-6111
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- Citations: 4
, 1996, Differential depletion of human respiratory tract antioxidants in response to ozone challenge, Vol: 25, Pages: 499-513, ISSN: 1071-5762
Smith SF, Benjamin A, Dewar A, et al., 1995, Effect of dexamethasone on carrageenin-induced inflammation in the lung, Mediators of Inflammation, Vol: 4, Pages: 273-281, ISSN: 1466-1861
To study the anti-inflammatory mechanisms of glucocorticoids, we have compared the effects of intratracheal carrageenin (2.5 mg) on control rats and those in which inflammation was subdued by prior dexamethasone treatment (10 mg/l in drinking water). Inflammation was maximal 48 h post-carrageenin. After dexamethasone, carrageenin caused tittle inflammation or oedema (wet lung (mg), n = 6, mean ± S.E.M.; control, 995 ± 51; carrageenin + dexamethasone, 1144 ± 83; compared with carrageenin alone, 1881 ± 198), but rats had more lung lavage neutrophils than those given carrageenin alone (PMN × 106 /lung, mean ± S.E.M.; control, 0.055 ± 0.003; carrageenin + dexamethasone, 8.54 ± 1.52; compared with carrageenin alone, 6.30 ± 1.71). Proteolysis and partial inactivation of the anti-inflammatory mediator, lipocortin 1 (Lcl), in carrageenin-instilled rats was offset in those also given dexamethasone, by increased Lc1 levels (intact Lc1 ng/ml lavage fluid, n = 4, mean ± S.E.M.; control 24 ± 6; carrageenin 15 ± 4; carrageenin + dexamethasone, 40 ± 15). Maintenance of sufficient intact (fully active) extracellular Lc1 may contribute to the actions of glucocorticoids.
SMITH SF, BENJAMIN A, DEWAR A, et al., 1995, EFFECT OF DEXAMETHASONE ON CARRAGEENAN-INDUCED INFLAMMATION IN THE LUNG, MEDIATORS OF INFLAMMATION, Vol: 4, Pages: 273-281, ISSN: 0962-9351
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- Citations: 13
SMITH SF, TETLEY TD, DATTA AK, et al., 1995, LIPOCORTIN-1 DISTRIBUTION IN BRONCHOALVEOLAR LAVAGE FROM HEALTHY-HUMAN LUNG - EFFECT OF PREDNISOLONE, JOURNAL OF APPLIED PHYSIOLOGY, Vol: 79, Pages: 121-128, ISSN: 8750-7587
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- Citations: 21
Cunningham AC, Milne DS, Wilkes J, et al., 1994, Constitutive expression of MHC and adhesion molecules by alveolar epithelial cells (type II pneumocytes) isolated from human lung and comparison with immunocytochemical findings., J Cell Sci, Vol: 107 ( Pt 2), Pages: 443-449, ISSN: 0021-9533
Highly purified populations of alveolar epithelial cells (type II pneumocytes) were isolated from human lung specimens. These cells were characterised histochemically, by demonstrating the presence of intracellular alkaline phosphatase, and morphologically, by electron microscopic demonstration of lamellar bodies and microvilli. Expression of the epithelial glycoprotein HEA-125, of MHC class I and class II (HLA-DR, -DP and -DQ) antigens and of the intercellular adhesion molecules ICAM-1, VCAM-1, LFA-3 and B7 was quantified by flow cytometry. Comparison was made between the expression of these molecules by isolated type II cells and by alveolar epithelium in normal human lung tissue after immunocytochemical staining of frozen sections of donor lung. Isolated type II pneumocytes expressed HEA-125 and class I MHC molecules and the class II MHC molecules HLA-DR and -DP; HLA-DQ was not detected. The intercellular adhesion molecule ICAM-1 was expressed constitutively at low levels but there was minimal expression of VCAM-1, LFA-3 and B7. It was not possible to differentiate type II cells from the predominant type I pneumocytes on frozen sections. Alveolar epithelium expressed HEA-125, class I MHC antigens, the class II molecules HLA-DR, and -DP and the intercellular adhesion molecule LFA-3. Expression of the adhesion molecules ICAM-1, VCAM-1 and B7 was variable. As with the isolates, HLA-DQ was not observed on alveolar epithelium. In conclusion, a reproducible method for the isolation of pure populations of human type II pneumocytes has been developed. These cells were not damaged by the isolation procedure. It is not known whether alveolar epithelium can present antigens to T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
TETLEY TD, 1993, PROTEINASE IMBALANCE - ITS ROLE IN LUNG-DISEASE, THORAX, Vol: 48, Pages: 560-565, ISSN: 0040-6376
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- Citations: 128
Tetley TD, 1993, New perspectives on basic mechanisms in lung disease. 6. Proteinase imbalance: its role in lung disease., Thorax, Vol: 48, Pages: 560-565, ISSN: 0040-6376
The hypothesis, some 30 years ago, that NE was the sole proteolytic agent responsible for the development of emphysema seems naive in retrospect. The availability of technology to measure NE facilitated the early research into the relationship between NE and lung disease. Despite an abundance of information on the activity of NE in the lung, it will probably require prospective studies in man with specific NE inhibitors or control at the gene level to establish a causal relationship between NE and lung disease. Parallel research has resulted in the isolation and characterisation of NE inhibitors other than PI and, indeed, alternative proteolytic enzymes that might contribute to lung disease. It is perhaps impossible now to think that a single proteinase, however omnipotent it may be, causes lung diseases as diverse as emphysema and fibrosis. An important aspect that is emerging is the interrelationship between proteolytic enzymes produced by different, or sometimes the same, cells that could potentiate tissue proteolysis. The evidence suggests that there is likely to be coordinated action between neutrophils, macrophages, and possibly mesenchymal proteinases which can activate or inactivate each other. In addition, one class of proteinases often appears able to proteolytically inactivate inhibitors of the opposite class, which presumably could amplify proteolysis if it occurred in vivo. Although the work on this aspect of proteinase activity is in its infancy, one suspects that part of the normal regulation of proteinase activity might include compartmentalisation. For example, the neutrophil stores proteinases before appropriate release and can inactivate PI to enable proteolytic action pericellularly, whereas degradation of extracellular matrix by macrophages requires interaction between the cell and matrix which is facilitated by cell receptor bound uPA. Disintegration of these "compartments" due to oedema, proteolysis, or for mechanical reasons could
Smith SF, Roberts NA, Guz A, et al., 1993, α-1-Proteinase inhibitor activity can be compromised by the choice of assay conditions, ISSN: 0300-5127
TETLEY TD, 1992, EMPHYSEMA REVISITED, RESPIRATORY MEDICINE, Vol: 86, Pages: 187-193, ISSN: 0954-6111
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- Citations: 6
Mistry R, Snashall PD, Guz A, et al., 1992, Isolation of a novel lung elastase inhibitor from sheep: A role in endotoxin-induced acute lung injury?, ISSN: 0954-6111
Mistry R, Snashall PD, Totty N, et al., 1991, Isolation and characterization of sheep alpha 1-proteinase inhibitor., Biochem J, Vol: 273 ( Pt 3), Pages: 685-690, ISSN: 0264-6021
Sheep plasma proteinase inhibitor, analogous to human alpha 1-proteinase inhibitor (alpha 1 PI), was isolated to homogeneity. Purification was achieved by using (NH4)2SO4 precipitation, concanavalin A-Sepharose chromatography, Mono Q ion-exchange chromatography and PAGE. Sheep alpha 1 PI had an Mr of 56,000, inhibited human leucocyte elastase, pig pancreatic elastase and bovine trypsin on a 1:1 molar basis and had a plasma concentration of 1.6 +/- 0.21 g/l (mean +/- S.D.). Amino acid/carbohydrate composition (15% glycosylated) was similar to that of human alpha 1 PI (16% glycosylated); N-terminal analysis to 31 residues revealed 48-52% identity between the human and sheep proteins. Sheep alpha 1 PI was susceptible to oxidative inactivation by chloramine-T. Re-activation with the use of methionine sulphoxide peptide reductase and dithiothreitol indicated the presence of a methionine residue at the active site. These results establish that sheep alpha 1 PI has functional and structural characteristics close to those of human alpha 1 PI.
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