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http://purl.uniprot.org/citations/22551156http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22551156http://www.w3.org/2000/01/rdf-schema#comment"

Background and purpose

Acute silencing of caveolin-1 (Cav-1) modulates receptor-mediated contraction of airway smooth muscle. Moreover, COX-2- and 5-lipoxygenase (5-LO)-derived prostaglandin and leukotriene biosynthesis can influence smooth muscle reactivity. COX-2 half-life can be prolonged through association with Cav-1. We suggested that lack of Cav-1 modulated levels of COX-2 which in turn modulated tracheal contraction, when arachidonic acid signalling was disturbed by inhibition of COX-2.

Experimental approach

Using tracheal rings from Cav-1 knockout (KO) and wild-type mice (B6129SF2/J), we measured isometric contractions to methacholine and used PCR, immunoblotting and immunohistology to monitor expression of relevant proteins.

Key results

Tracheal rings from Cav-1 KO and wild-type mice exhibited similar responses, but the COX-2 inhibitor, indomethacin, increased responses of tracheal rings from Cav-1 KO mice to methacholine. The phospholipase A₂ inhibitor, eicosatetraynoic acid, which inhibits formation of both COX-2 and 5-LO metabolites, had no effect on wild-type or Cav-1 KO tissues. Indomethacin-mediated hyperreactivity was ablated by the LTD₄ receptor antagonist (montelukast) and 5-LO inhibitor (zileuton). The potentiating effect of indomethacin on Cav-1 KO responses to methacholine was blocked by epithelial denudation. Immunoprecipitation showed that COX-2 binds Cav-1 in wild-type lungs. Immunoblotting and qPCR revealed elevated levels of COX-2 and 5-LO protein, but not COX-1, in Cav-1 KO tracheas, a feature that was prevented by removal of the epithelium.

Conclusion and implications

The indomethacin-induced hypercontractility observed in Cav-1 KO tracheas was linked to increased expression of COX-2 and 5-LO, which probably enhanced arachidonic acid shunting and generation of pro-contractile leukotrienes when COX-2 was inhibited."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.org/dc/terms/identifier"doi:10.1111/j.1476-5381.2012.02014.x"xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Sharma P."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Basu S."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Halayko A.J."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Mitchell R.W."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Ryu M.H."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Yeganeh B."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Mutawe M.M."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/author"Maltby S.A."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/name"Br J Pharmacol"xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/pages"548-560"xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/title"Epithelium-dependent modulation of responsiveness of airways from caveolin-1 knockout mice is mediated through cyclooxygenase-2 and 5-lipoxygenase."xsd:string
http://purl.uniprot.org/citations/22551156http://purl.uniprot.org/core/volume"167"xsd:string
http://purl.uniprot.org/citations/22551156http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22551156
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