| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Recently, cytokines homologous to IL-17 have been identified by database searching. Five new family members have been identified, namely IL-17B,IL-17C,IL-17D,IL-17E/IL-25,and IL-17F, in which these molecules possess 18-30% homology to IL-17. Among IL-17 family cytokines, it has been shown that the in vivo and in vitro biological activities of IL-25 are markedly different from those described for IL-17 and other IL-17 family cytokines. The expression of IL-25 results in the expansion of eosinophils through the production of IL-5 from an unidentified non-T cell population, whereas other IL-17 family cytokines induce the expansion of neutrophils. In addition, IL-25 induces elevated gene expression of IL-4 and IL-13 in multiple tissues and the resultant Th2-type immune responses, including increased serum IgE levels and pathological changes with eosinophilic infiltrates.
In the present study, we first show that mast cells are also potent IL-25-producing cells. We found that when bone marrow-derived mast cells(BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min in a calcineurin-dependent manner and the levels of IL-25 mRNA were comparable to that of activated Th2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting.
We also investigated the role of IL-25 in allergic airway inflammation. We found that IL-25 mRNA was induced in the airways in the sensitized mice upon the inhaled allergen challenge. Moreover, the enforced expression of IL-25 in the lung in CC10-IL-25 transgenic mice resulted in the enhanced antigen-induced airway inflammation. These results suggest that IL-25 is involved in the enhancement of allergic airway inflammation.
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