Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea‐pigs

Leick-Maldonado, Edna A.; Kay, Fernando Uliana; Leonhardt, M.; Kasahara, David I.; Prado, Carla M.; Fernandes, F. T.; Martins, Mílton A.; Tibério, Iolanda de Fátima Lopes Calvo

doi:10.1111/j.1365-2222.2004.01854.x

Cited by 59 publications

(96 citation statements)

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“…In addition, we have previously shown (28) that chronic L-NAME treatment in this animal model reduced the exhaled NO by ϳ50% compared with controls. The L-NAME treatment began 24 h after the forth inhalation to avoid interference with the sensitization since in this period animals have already been sensitized (IgG 1 title 1:320) (16). In fact we had previously evaluated the effects of this approach of L-NAME treatment in the sensitization process, and we observed that this treatment did not interfere with the sensitization (26,27,28).…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

Angeli¹,

Prado²,

Xisto³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionmentioning

confidence: 99%

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

Angeli¹,

Prado²,

Xisto³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…20). Excess NO has been correlated with the degree of airway inflammation in asthma patients and animal models (27,32,39,50,51,56). Although the role of elevated NO in asthma is accepted, the relative contribution of each of the NOS isoforms to the production of NO in asthma is unclear.…”

Section: Discussionmentioning

confidence: 99%

Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma

Klein

Weigel

Buford

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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(NOS), is an important mediator of lung inflammation in allergic asthma. Asymmetric dimethylarginine (ADMA), a competitive endogenous inhibitor of NOS, is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Elevated ADMA has been shown to affect lung function in mice, and by inhibiting NOS it alters NO and reactive oxygen species production in mouse lung epithelial cells. However, the effects of altered ADMA levels during lung inflammation have not been explored. A model of allergen-induced airway inflammation was utilized in combination with the modulation of endogenous circulating ADMA levels in mice. Airway inflammation was assessed by quantifying inflammatory cell infiltrates in lung lavage and by histology. Lung DDAH expression was assessed by quantitative PCR and immunohistochemistry. Nitrite levels were determined in lung lavage fluid as a measure of NO production. iNOS expression was determined by immunohistochemistry, immunofluorescence, Western blot, and quantitative PCR. NF-B binding activity was assessed by a transcription factor binding assay. Allergen-induced lung inflammation was potentiated in mice with elevated circulating ADMA and was reduced in mice overexpressing DDAH. Elevated ADMA reduced nitrite levels in lung lavage fluid in both allergenchallenged and control animals. ADMA increased iNOS expression in airway epithelial cells in vivo following allergen challenge and in vitro in stimulated mouse lung epithelial cells. ADMA also increased NF-B binding activity in airway epithelial cells in vitro. These data support that ADMA may play a role in inflammatory airway diseases such as asthma through modulation of iNOS expression in lung epithelial cells. airway; dimethylarginine dimethylaminohydrolase; inducible nitric oxide synthase ONE OF THE KEY PATHOGENIC features of asthma is the infiltration and activation of inflammatory cells in the airways (6,17,21,22). Lung inflammation in allergic asthma is induced by a cascade of reactions involving several mediators including nitric oxide (NO) (55). NO is a highly reactive radical formed by the metabolism of the semi-essential amino acid L-arginine by nitric oxide synthase (NOS) (29). There are three predominant NOS isoforms. The constitutive isoforms of NOS (cNOS) are expressed mainly in nonadrenergic noncholinergic nerves (nNOS), in endothelial cells (eNOS), and in airway epithelium (nNOS and eNOS) (2,19,29,62), and are involved in the physiological regulation of the airway by local production of small amounts of NO. The third isoform (iNOS) is induced following exposure to proinflammatory cytokines and is expressed in epithelial and inflammatory cells of the airway (57). Although it is known that NO plays a role in asthma by contributing to pulmonary inflammation after allergen challenge (49, 69), the contribution of each of the NOS isoforms to inflammation in the airway is unclear. Pharmacological inhibitors of NOS have been used to study the role of specific NOS isoforms in asthma and have provided support for iNOSmediate...

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“…Among downstream lipid mediators of 5-lipoxygenase, cysteinyl LTs (LTC 4 , D 4 , and E 4 ), originally termed slow-reacting substance of anaphylaxis have been reported to increase vascular permeability, and bronchial smooth muscle constriction, through two distinct types of receptors, CysLT1 and CysLT2. Although several CysLT1 antagonists such as zafirlukast, montelukast, and pranlukast are currently used for treatment of asthmatic patients, the effect is heterogeneous, and a significant number of patients are resistant to the CysLT antagonist treatment (16). Leukotriene B 4 (LTB 4 ), another eicosanoid derived from 5-lipoxygenase pathway of arachidonic acid, has well-documented potent chemotactic activity toward granulocytes (17).…”

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confidence: 99%

Absence of Leukotriene B4 Receptor 1 Confers Resistance to Airway Hyperresponsiveness and Th2-Type Immune Responses

Terawaki

Yokomizo²,

Nagase³

et al. 2005

The Journal of Immunology

156

147

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Bronchial asthma is an increasingly common disorder that remains poorly understood and difficult to manage. The disease is characterized by airway hyperresponsiveness, chronic inflammation, and mucus overproduction. Based on the finding that leukotriene B4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an OVA-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation, and hyperplasia of goblet cells. Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice. Peribronchial lymph node cells of sensitized BLT1-null mice showed much attenuated proliferation and production of Th2 cytokines upon re-stimulation with Ag in vitro. Thus, LTB4-BLT1 axis is required for the development of Th2-type immune response, and blockade of LTB4 functions through BLT1 would be novel and useful in the effort to ameliorate bronchial asthma and related Th2-biased immune disorders.

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Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea‐pigs

Abstract: Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration.

Cited by 59 publications

References 48 publications

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma

Absence of Leukotriene B4 Receptor 1 Confers Resistance to Airway Hyperresponsiveness and Th2-Type Immune Responses

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