| Co-Investigator(Kenkyū-buntansha) |
TSUTSUI Hiroko HYOGO COLLEGE OF MEDICINE, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (40236914)
YOSHIMOTO Tomohiro HYOGO COLLEGE OF MEDICINE, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (60241171)
OKAMURA Haruki HYOGO COLLEGE OF MEDICINE, FACULTY OF MEDICINE, PROFESSOR(2001) (60111043)
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| Research Abstract |
IL-18 was originally discovered as an IFN-γ-inducing factor. However, later studies revealed its potential to induce T cells to produce Th2-related cytokines, when it acts on T cells without IL-12. In the presence of IL-2,IL-18 stimulates T cells to produce Th2-cytokines. In the presence of IL-3,IL-18 stimulates basophils/ mast cells to produce Th2-cytokines, chemokines and chemical mediators. Through these studies, we could assume that local over-production of IL-18 may have capacity to induce innate-type atopy. In 2001,we could reveal that caspase-1 transgenic mice, that over expressed IL-18 in their keratinocytes, develop AD without their exposure to allergen. Furthermore, we showed that Stat 6-depeleted Caspase-1 transgenic mice developed compaciable level of AD even though they displayed no IgE in their sera. In 2002,we studied how systemic injection of IL-18 induces IgE response in normal mice. We found that IL-18 stimulates NKT cells, that constitutively express IL-18R, to produce IL-4 and to express CD40L in vivo. We also found such IL-18-stimulated NKT cells in collaboration with conventional T cells induce B cells to produce IgE. Finally, in 2003,we demonstrated that Th1 cell-transferred mice develop airway inflammation and hyperresponsiveness in response to nasully administered Ag plus IL-18. Therfore IL-18 may become important phamacological target molecule for the development of effective drugs for allergic disorders.
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