Interactions between leukotriene C4 and interleukin 13 signaling pathways in a mouse model of airway disease

Jaime Chavez, Hays W.J. Young, David Corry, Michael W. Lieberman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Context. - During an asthmatic episode, leukotriene C4 (LTC 4) and interleukin 13 (IL-13) are released into the airways and are thought to be central mediators of the asthmatic response. However, little is known about how these molecules interact or affect each other's signaling pathway. Objective. - To determine if the LTC4 and IL-13 signaling pathways interact with each other's pathways. Design. - We examined airway responsiveness, cysteinyl LTs (Cys-LTs), and Cys-LT and IL-13 receptor transcript levels in wild-type mice and in mice that were deficient in γ-glutamyl leukotrienase (an enzyme that converts LTC4 to LTD4), STAT6 (signal transducer and activator of transcription 6 [a critical molecule in IL-13 signaling]), and IL-4Rα (a subunit of the IL-13 receptor). Results. - Wild-type (C57BL/129SvEv) and γ-glutamyl leukotnenase-deficient mice showed increased airway responsiveness after intranasal instillation of IL-13; similar results were observed after intranasal instillation of IL-13 or LTC4 in a second wild-type strain (BALB/c). Interleukin 13 treatment reduced levels of Cys-LTs in bronchoalveolar lavage fluid. This change was unaccompanied by changes in other arachidonic acid metabolites or in RNA transcript levels of enzymes associated with Cys-LT synthesis. Interleukin 13 treatment also increased transcript levels of the Cys-LT 1 and Cys-LT 2 receptors, while LTC4 increased transcript levels of the α1 chain of the IL-13 receptor. Furthermore, IL-4Rα-deficient mice had increased airway responsiveness to LTC 4 but not to IL-13, whereas STAT6-deficient mice failed to respond to either agonist. Conclusions. - These findings indicate that LTC4 and IL-13 are dependent on or signal through STAT6 to increase airway responsiveness and that both agonists regulate expression of each other's receptors.

Original languageEnglish (US)
Pages (from-to)440-446
Number of pages7
JournalArchives of Pathology and Laboratory Medicine
Volume130
Issue number4
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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