Cytosolic DNA fragments represent pathogen and danger associated molecular patterns and induces a cascade of innate immune responses in the cells. Excessive cytosolic DNA can enhance chronic inflammation predominantly by activating inflammasomes therefore contributing to the pathogenesis of chronic diseases such as psoriasis. Psoriasis associated non-protein coding RNA induced by stress (PRINS) is a long non-coding RNA, which has already been associated with psoriasis susceptibility and cellular stress response; however its precise mechanism was less studied. The aim of this study was to identify the role of PRINS in psoriasis associated inflammatory reactions, which could explain the importance of its high expression in psoriatic uninvolved epidermis. The synthetic DNA analogue poly(dA:dT) transfection was used to induce inflammatory reactions in normal human epidermal keratinocytes (NHEKs), and expression of inflammatory cytokines was measured by real-time RT-PCR and ELISA. Poly(dA:dT) transfection induced the expression and secretion of IL-1a, IL-1b, IL-6 and TNF-a, while decreased PRINS expression was detected. To study the possible role of PRINS in the poly(dA:dT) induced cytokine production of NHEKs we forced its expression by vector based method. Overexpression of PRINS reduced the poly(dA:dT)-induced IL-6 production, but did not affect the production of the other investigated cytokines. In silico analysis revealed a putative interaction site between PRINS and the mRNA of IL-6 and the interaction was confirmed by an in vitro binding assay. On cellular level, destruction of the IL-6 mRNA binding site in the PRINS sequence lead to the loss of PRINS' ability to inhibit IL-6 production. These results show a restrictive effect of PRINS in inflammatory processes, and indicate the role of its higher expression in psoriatic uninvolved epidermis.

Seoul-t'ukpyolsi, Republic of Korea Here we investigated effects of anacardic acid (AA) on the regulation of lipogenesis in differentiated human adipocytes, and elucidated possible epigenetic mechanisms via p300 histone acetyltransferase activity. To investigate the role of histone acetylation in lipogenesis regulation, we evaluated triglyceride (TG) contents, expression of key lipogenic enzyme acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c) in primary cultured adipocytes isolated from subcutaneous adipose tissues. Treatment of AA or knockdown of p300 by using transient transfection of p300 siRNA led to significant reduction of TG contents, SREBP-1c and ACC expression, indicating that p300 mediates SREBP-1, ACC expression, and corollary lipid production. While p300 overexpression by p300WT was associated with significantly enhanced activity of SREBP1-908luc promoter, the SREBP1-908luc promoter activity was significantly reduced in the presence of p300DHAT. In addition, we performed a promoter assay using HEK293T cells treated with AA or TSA. While the SREBP1-908luc promoter activity was significantly decreased by AA, but significantly increased by TSA treatment. These findings suggest that histone acetyltransferase activity of p300, not a p300 expression per se, is critical for the transcriptional regulation of SREBP-1 and p300HAT inhibitors such as AA could be employed as anti-obesity modalities.