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Effect of an inhibitor of Jun N-terminal protein kinase, SP600125, in single allergen challenge in sensitized rats.

https://arctichealth.org/en/permalink/ahliterature15159
Source
Immunology. 2004 Jul;112(3):446-53
Publication Type
Article
Date
Jul-2004
Author
Paul R Eynott
Li Xu
Brydon L Bennett
Alistair Noble
Sum-Yee Leung
Puneeta Nath
David A Groneberg
Ian M Adcock
K Fan Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Source
Immunology. 2004 Jul;112(3):446-53
Date
Jul-2004
Language
English
Publication Type
Article
Keywords
Allergens - pharmacology
Animals
Anthracenes - pharmacology
Asthma - immunology
Bronchoalveolar Lavage Fluid - immunology
Cell Count
Cytokines - immunology
Enzyme Activation
Eosinophils - immunology
JNK Mitogen-Activated Protein Kinases
Leukocyte Count
Leukocytes, Mononuclear - immunology
Lung - enzymology - immunology
MAP Kinase Kinase 4
Macrophages - immunology
Male
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors - metabolism
Mitogen-Activated Protein Kinases - metabolism
Models, Animal
Neutrophils - immunology
Ovalbumin
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
p38 Mitogen-Activated Protein Kinases
Abstract
Jun N-terminal kinase (JNK) has been implicated in the pathogenesis of inflammatory diseases including asthma. We examined the effect of SP600125 (anthra [1,9-cd] pyrazol-6 (2H)-one), a novel inhibitor of JNK in a model of asthma. Brown-Norway rats were sensitized to ovalbumin and treated with SP600125 intraperitoneally (90 mg/kg in total). SP600125 inhibited allergen-induced, increased activity of phosphorylated c-jun but not of phosphorylated-MAPKAPK2, indicative of activation of p38 MAPK, in the lung. SP600125 inhibited macrophage (P
PubMed ID
15196213 View in PubMed
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Effects of ciclesonide and fluticasone propionate on allergen-induced airway inflammation and remodeling features.

https://arctichealth.org/en/permalink/ahliterature15059
Source
J Allergy Clin Immunol. 2005 May;115(5):989-96
Publication Type
Article
Date
May-2005
Author
Sum Yee Leung
Paul Eynott
Puneeta Nath
Kian Fan Chung
Author Affiliation
Department of Thoracic Medicine, National Heart & Lung Institute, Imperial College, London, UK.
Source
J Allergy Clin Immunol. 2005 May;115(5):989-96
Date
May-2005
Language
English
Publication Type
Article
Keywords
Administration, Inhalation
Allergens - adverse effects
Androstadienes - administration & dosage - therapeutic use
Animals
Anti-Allergic Agents - administration & dosage - therapeutic use
Body Weight - drug effects
Comparative Study
Corticosterone - blood
Dose-Response Relationship, Drug
Eosinophils - immunology
Epithelial Cells - drug effects
Male
Muscle, Smooth - drug effects
Ovalbumin - adverse effects
Pregnenediones - administration & dosage - therapeutic use
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Respiratory Hypersensitivity - drug therapy - etiology - metabolism
Respiratory System - drug effects - pathology
T-Lymphocytes - immunology
Abstract
BACKGROUND: Several topical corticosteroids are available as anti-inflammatory treatment for asthma. Their comparative effects on allergic inflammation and airway remodeling are unclear. OBJECTIVE: We compared the effects of ciclesonide with those of fluticasone propionate in a Brown Norway rat model of chronic allergic asthma. METHODS: Rats sensitized and exposed to ovalbumin (OVA) were treated with dry powder vehicle, ciclesonide, or fluticasone (0.01, 0.03, and 0.1 mg/kg administered intratracheally) 24 hours and 1 hour before each of 6 OVA exposures. In a second protocol we administered 0.1 mg/kg ciclesonide or fluticasone only after the third OVA exposure. RESULTS: Ciclesonide at all doses inhibited the allergen-induced increase in airway eosinophils and T cells, reduced goblet cell hyperplasia, and decreased 5-bromo-2'-deoxyuridine-immunoreactive airway smooth muscle (ASM) and epithelial cells. At 0.03 and 0.1 mg/kg ciclesonide, bronchial hyperresponsiveness (BHR) was also inhibited. Fluticasone did not attenuate allergen-induced BHR, despite inhibiting airway eosinophils and T cells, goblet cell hyperplasia, and 5-bromo-2'-deoxyuridine-immunoreactive ASM and epithelial cells. Fluticasone (0.1 mg/kg) caused a significant reduction in body weight (9%) compared with ciclesonide (0.1 mg/kg). Ciclesonide did not change plasma corticosterone levels, whereas fluticasone (0.1 mg/kg) reduced them. In the second protocol both fluticasone and ciclesonide inhibited BHR, bronchial inflammation, goblet cell hyperplasia, and ASM proliferation. CONCLUSION: Ciclesonide potently inhibited chronic allergic inflammation, remodeling, and BHR without having an effect on body weight and the hypothalamic-pituitary-adrenal axis. Fluticasone prevented airway inflammation but not BHR, but both fluticasone and ciclesonide are effective at reversal of BHR, inflammation, and remodeling features.
PubMed ID
15867856 View in PubMed
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Role of nitric oxide in chronic allergen-induced airway cell proliferation and inflammation.

https://arctichealth.org/en/permalink/ahliterature15302
Source
J Pharmacol Exp Ther. 2003 Jan;304(1):22-9
Publication Type
Article
Date
Jan-2003
Author
Paul R Eynott
Niko Paavolainen
David A Groneberg
Alistair Noble
Michael Salmon
Puneeta Nath
Sum-Yee Leung
K Fan Chung
Author Affiliation
National Heart and Lung Institute, Imperial College School of Science, Technology and Medicine, London, United Kingdom.
Source
J Pharmacol Exp Ther. 2003 Jan;304(1):22-9
Date
Jan-2003
Language
English
Publication Type
Article
Keywords
Actins - biosynthesis
Allergens - toxicity
Animals
Bromodeoxyuridine - diagnostic use
Bronchoalveolar Lavage Fluid - cytology
Cell Count
Cell Division - drug effects
DNA - biosynthesis
Enzyme Inhibitors - pharmacology
Eosinophils - drug effects - metabolism
Homoarginine - analogs & derivatives - pharmacology
Immunoglobulin E - biosynthesis
Immunohistochemistry
Inflammation - chemically induced - pathology
Isoenzymes - metabolism
Lymphocytes - drug effects
Male
Muscle, Smooth - cytology - drug effects - pathology
Nitric Oxide - physiology
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase Type III
Ovalbumin - immunology
Rats
Rats, Inbred BN
Respiratory System - cytology - drug effects - pathology
Abstract
Chronic cellular inflammation and airway wall remodeling with subepithelial fibrosis and airway smooth muscle thickening are features of chronic asthma. We determined the role of nitric oxide in the pathogenesis of allergen-induced airway cell proliferation and inflammation by studying the effects of a relatively selective prodrug inhibitor of nitric-oxide synthase type 2 (NOS2), L-N6-(1-iminoethyl)-lysine-5-tetrazole amide (SC-51). Brown-Norway rats were sensitized to ovalbumin and were exposed to ovalbumin aerosol every 3rd day on six occasions and were treated orally with either vehicle or SC-51 (10 mg. kg(-1); 12 doses). We measured inflammatory cell accumulation in the airways and proliferation of cells by incorporation of bromodeoxyuridine. There was an increase in the total number of airway smooth muscle cells expressing bromodeoxyuridine from 1.3% of airway smooth muscle cells in saline exposed to 5.4% after allergen-exposure (P
PubMed ID
12490571 View in PubMed
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