PFN1 Prevents Psoriasis Pathogenesis through IκBζ Regulation.

PFN1 is an actin-binding protein that regulates actin polymerization, cell proliferation, apoptosis, angiogenesis, and carcinogenesis. Its dysregulation has been reported in diverse pathologic diseases; however, the role of PFN1 in psoriasis has not yet been elucidated. In this study, we show that PFN1 expression is increased in both skin and serum of patients with psoriasis. PFN1 was markedly expressed in the epidermis of psoriatic lesions, and its expression positively correlated with psoriasis severity. IL-17A treatment of keratinocytes increased PFN1 expression, whereas TNF-α induced PFN1 expression and secretion. In addition, knockdown of PFN1 with short hairpin RNA resulted in an altered expression of psoriasis-associated inflammatory markers, HBD2, S100A7, S100A9, and Ki-67, and recombinant PFN1 suppressed the IL-17A‒induced inflammatory response in keratinocytes. Interestingly, recombinant PFN1 also suppressed IL-17A‒induced IκBζ, an important player in immune response in psoriasis. Collectively, our results show that PFN1 acts as a negative regulator of psoriatic inflammation through the suppression of IκBζ and that the balanced level of PFN1 is important for IκBζ regulation. Thus, the expression of PFN1 can be used as a biomarker for psoriasis severity, and it can be considered as a possible target for the treatment of psoriasis.

A New Histone Deacetylase Inhibitor, MHY219, Inhibits the Migration of Human Prostate Cancer Cells via HDAC1.

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP (IC50=0.67 µM) than in DU145 cells (IC50=1.10 µM) and PC3 cells (IC50=5.60 µM) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.