Linked Life Data

15153527

Source:http://linkedlifedata.com/resource/pubmed/id/15153527

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-5-21
pubmed:abstractText
Mitogen-activated protein kinase (MAPK) signaling cascade plays a pivotal role in the activation of inflammatory cells. Recent findings revealed that the activity of p42/44 MAPK (also known as extracellular signal-regulated kinase (ERK)) in the lungs was significantly higher in asthmatic mice than in normal controls. We hypothesized that inhibition of ERK activity may have anti-inflammatory effects in allergic asthma. BALB/c mice were sensitized with OVA and, upon OVA aerosol challenge, developed airway eosinophilia, mucus hypersecretion, elevation in cytokine and chemokine levels, up-regulation of VCAM-1 expression, and airway hyperresponsiveness. Intraperitoneal administration of U0126, a specific MAPK/ERK kinase inhibitor, significantly (p < 0.05) inhibited OVA-induced increases in total cell counts, eosinophil counts, and IL-4, IL-5, IL-13, and eotaxin levels recovered in bronchoalveolar lavage fluid in a dose-dependent manner. U0126 also substantially (p < 0.05) reduced the serum levels of total IgE and OVA-specific IgE and IgG1. Histological studies show that U0126 dramatically inhibited OVA-induced lung tissue eosinophilia, airway mucus production, and expression of VCAM-1 in lung tissues. In addition, U0126 significantly (p < 0.05) suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine in a dose-dependent manner. Western blot analysis of whole lung lysates shows that U0126 markedly attenuated OVA-induced tyrosine phosphorylation of ERK1/2. Taken together, our findings implicate that inhibition of ERK signaling pathway may have therapeutic potential for the treatment of allergic airway inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7053-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15153527-Animals, pubmed-meshheading:15153527-Anti-Inflammatory Agents, pubmed-meshheading:15153527-Asthma, pubmed-meshheading:15153527-Bronchial Hyperreactivity, pubmed-meshheading:15153527-Bronchoalveolar Lavage Fluid, pubmed-meshheading:15153527-Butadienes, pubmed-meshheading:15153527-Cytokines, pubmed-meshheading:15153527-Disease Models, Animal, pubmed-meshheading:15153527-Enzyme Inhibitors, pubmed-meshheading:15153527-Eosinophils, pubmed-meshheading:15153527-Immunoglobulin G, pubmed-meshheading:15153527-Male, pubmed-meshheading:15153527-Mice, pubmed-meshheading:15153527-Mice, Inbred BALB C, pubmed-meshheading:15153527-Mitogen-Activated Protein Kinases, pubmed-meshheading:15153527-Mucus, pubmed-meshheading:15153527-Nitriles, pubmed-meshheading:15153527-Ovalbumin, pubmed-meshheading:15153527-Phosphorylation, pubmed-meshheading:15153527-Vascular Cell Adhesion Molecule-1
pubmed:year
2004
pubmed:articleTitle
Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model.
pubmed:affiliation
Department of Pharmacology, National University of Singapore, Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't