Leukotriene enhanced allergic lung inflammation through induction of chemokine production

Kihyuk Shin, Jung Joo Hwang, Bo In Kwon, Farrah Kheradmand, David Corry, Seung Hyo Lee

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The leukotrienes (LTs) enhance allergen- and interleukin (IL)-13-dependent allergic lung inflammatory disease. However, the precise requirement of LTs and the mechanism by which they elicit allergic lung responses remain uncertain. To clarify the involvement of LTs in respiratory allergen- and IL-13-induced experimental asthma and elucidate the underlying mechanisms of LTs-mediated enhanced allergic asthma, we investigated the role of LTs in two models of allergic inflammation: intranasal Aspergillus protease allergen and recombinant IL-13-induced T helper type 2 (Th2) cell-mediated inflammation, and also examined Th2-related chemokines downstream of LTs signaling. 5-Lipoxygenase (5-LO)-deficient mice exposed to short-term intranasal Aspergillus protease allergen showed attenuated airway inflammation, decreased airway hyper-responsiveness and reduced bronchoalveolar eosinophilia when compared to wild-type mice. However, this phenotype was less apparent using long exposure to the same allergen. 5-LO-deficient mice exposed to intranasal rIL-13 also showed attenuated phenotypes of allergic asthma via significant reduction in Th2-specific chemokines, CCL7 and CCL17 production and decreased Th2 cells recruitment to the lungs. Addition of leukotriene B4 (LTB4) and LTC4 to the airways of 5-LO-deficient mice resulted in the rescue of rIL-13-induced experimental asthma. Furthermore, LTs addition to rIL-13 synergistically enhanced the production of Th2-specific chemokines in the lung and inflammatory responses. Therefore, our findings suggest that LTs complement allergens and their downstream cytokine (e.g., IL-13) induced Th2 inflammation by enhancing the induction of Th2 chemokines.

Original languageEnglish (US)
Pages (from-to)233-244
Number of pages12
JournalClinical and Experimental Medicine
Volume15
Issue number3
DOIs
StatePublished - Aug 3 2015

Keywords

  • Chemokines
  • Interleukin-13 (IL-13)
  • Leukotrienes (LTs)
  • Lung inflammation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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