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.