Developing an Anti-Psoriatic Therapy by Blocking the Proliferation and Inflammatory Effects of IFI27

Psoriasis is a multifactorial hyperproliferative inflammatory skin disease characterized by hyperproliferation of keratinocytes, aberrant epidermal differentiation, and infiltration of inflammatory cells. In recent years, most research has focused on immunopathogenesis; however, interest in the role of keratinocytes has also been renewed. IFI27, belonged to a family of small interferon-alpha (IFN-α)-inducible genes, was first reported over-expressed in breast carcinoma in 1993, and following studies also demonstrated the significant increase of IFI27 expression in psoriasis and certain epithelial cancers. Although it is highly speculated that IFI27 might be a marker for the proliferation of skin keratinocytes, however, the function of IFI27 has not yet been fully investigated. The experimental results from our NSC102-2314-B-182-017-study showed that the IFI27 expression of epidermal keratinocytes could be induced time- and dose-dependently by EGF and TNF-α, two major factors found to be significantly increased in psoriatic patients. IFI27 knockdown in epidermal keratinocytes resulted in S-phase arrest that was mediated by the impaired formation and CDK1 and cyclin A. Over-expression of IFI27 in keratinocytes, on the other hand, accelerated the cell proliferation rate, confirming the proliferating function of IFI27 in keratinocytes which should play an important role in the pathogenesis of psoriasis. In addition, we have successfully established the imiquimod-induced psoriasis in mice model. Our preliminary data showed that treatment with IFI27 siRNA might also have anti-inflammatory and anti-angiogenic effects. Therefore, we proposed in this two years study: 1 st year--The regulation and function of IFI27 will be further studied. 2 nd year--The therapeutic efficacy of IFI27 siRNA will be investigated on imiquimod-induced mice model. This study will help us to understand the function of IFI27 in psoriasis and based on this understanding, hopefully, we can develop a new IFI27-targeted therapy for psoriasis.

Project ID:PC10308-1880
External Project ID:MOST103-2314-B182-029