| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Research Abstract |
IL-27, a member of IL-12 cytokine family, primes Th1 cell differentiation, while it suppresses Th17 cell development. We have previously reported that serum IL-27 levels are elevated in psoriatic patients and that IL-27 greatly induces in vitro production of Th1-type chemokines through STAT1 activation. In this study, to further investigate the in vivo role of IL-27 in the pathogensis of psoriasis, we induced psoriasis-like inflammation on mouse back skin with topical application of imiquimod, and continuously injected IL-27 or PBS subcutaneously. Imiquimod-treated skin showed the increase of IL-27 mRNA levels and the infiltration of IL-27-producing cells in the papillary dermis. The injection of IL-27 to the imiquimod-treated skin exacerbated the disease compared with PBS injection. The IL-27 injection further augmented mRNA levels of IFN-〓, CXCL9, CXCL10, CXCL11, and TNF-〓, without altering those of IL-17A, IL-17F, IL-22, and CCL20. Finally, IL-27 antagonism attenuated the upregulation of IFN-〓, CXCL9, CXCL10, CXCL11 and TNF-〓 mRNA levels, and induced clinical and histological improvement in the imiquimod-treated skin. These results indicate that IL-27 would act in aproinflammatory manner, and thereby exacerbates the psoriasis-like skin inflammation induced by imiquimod.
|
