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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-11-10
pubmed:abstractText
To identify proteins that might play an important role in allergen-induced asthma, we analyzed lung extracts prepared from allergen (ovalbumin)-challenged animals in a mouse model of this condition. The combination of two-dimensional gel electrophoresis and mass spectrometry revealed that annexin-1, a 37 kDa anti-inflammatory protein that inhibits the activity of cytosolic phospholipase A(2) (cPLA(2)), was down-regulated by allergen challenge in the lungs of ovalbumin-sensitized mice. Immunoblot analysis showed that this effect of ovalbumin challenge was attributable to proteolytic cleavage of annexin-1. The ovalbumin-induced degradation of annexin-1 was blocked by pretreatment of mice with the antioxidant N-acetylcysteine (NAC) or with sodium selenite, both of which have previously been shown to exert anti-inflammatory effects in this asthma model. Ovalbumin challenge also both increased the expression of cPLA(2) in lung tissue and reduced the extent of the interaction between cPLA(2) and annexin-1, and these effects were inhibited by NAC or selenite. Moreover, the concentrations of cysteinyl leukotrienes in bronchoalveolar lavage fluid and of leukotriene B(4) in lung tissue were increased by ovalbumin challenge in a NAC- or selenite-sensitive manner. Together, these results suggest that allergen-induced oxidative stress results in proteolysis of annexin-1 and consequent up-regulation of cPLA(2) activity and leukotriene production in this mouse model of asthma, and that the anti-inflammatory effects of selenite may provide a basis for the development of new antiasthmatic drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1615-9853
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3328-34
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Allergen-induced proteolytic cleavage of annexin-1 and activation of cytosolic phospholipase A2 in the lungs of a mouse model of asthma.
pubmed:affiliation
Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't