Cytosolic
DNA fragments are recognized as pathogen- and danger-associated molecular patterns that induce a cascade of innate immune responses. Moreover, excessive cytosolic
DNA can enhance chronic
inflammation, predominantly by activating
inflammasomes, and thereby 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 been shown to be associated with
psoriasis susceptibility and cellular stress responses; however, the precise mechanism of its action has not been determined. Here, we provide evidence that, in addition to
inflammasome activation, cytosolic
DNA induces intracellular inflammatory reactions while decreasing PRINS gene expression. Furthermore, PRINS overexpression can ameliorate the inflammatory-mediator production of keratinocytes induced by cytosolic
DNA. Overexpression of PRINS resulted in decreased
interleukin-6 (IL-6) and
chemokine (C-C motif)
ligand 5 (CCL-5) expression and secretion. In silico analysis predicted direct binding sites between PRINS and the mRNAs, which was confirmed by an in vitro binding assay and on cellular level. Our results indicated that PRINS binds directly to the mRNAs of
IL-6 and CCL-5 at specific binding sites and eventually destabilizes these mRNAs, leading to a decrease in their expression and secretion of the corresponding
proteins. These results may indicate a restrictive role for PRINS in inflammatory processes.