451 Anacardic acid reduces lipogenesis in human differentiated adipocytes via inhibition of histone acetylation

Abstract

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.