372 Mechanism of cytosolic nucleic acid-induced CX3CL1 expression of human keratinocytes

Psoriasis is a multifactorial, chronic inflammatory skin disease, the development of which affected by both genetic and environmental factors. Cytosolic nucleic acid fragments, recognized as pathogen- danger-associated molecular patterns, are highly abundant in psoriatic skin. It known that exhibits increased levels CX3CL1 (fractalkine) compared to healthy Recently we carried out qPCR array containing 84 psoriasis relevant genes identify showing altered expression upon analogue treatment. One largest transcriptional changes was CX3CL1. Our aim investigate mechanism how psoriasis-associated high free influence production keratinocytes. To induce processes, normal human epidermal keratinocytes (NHEK) were transiently transfected with synthetic dsDNA poly(dA:dT) dsRNA poly(I:C) or treated psoriasis-related cytokines (TNFα, IL-17A, IL-12). Nucleic analogues caused elevated mRNA levels, but different degree, however, cytokine treatments had no effect on transcription. clarify receptors pathways play role acid-induced keratinocytes, silenced several used specific inhibitors decrease activity signalling pathways. Detection showed silencing IFH1, RIG1, cGAS inhibition p38, STAT resulted results suggest acids epithelial through IFIH1, RIG1 contribute level this also seen psoriasis.