Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with. | Bak and Mikkelsen Journal of Biomedical Science 2010 17 53 http content 17 1 53 a NSC The cost of publication In Journal of Blomodlcal Sctonca Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE REVIEW Open Access Regulation of cytokines by small RNAs during skin inflammation Rasmus O Bak and Jacob G Mikkelsen Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production orchestrated by activated T-cells homing to the skin is believed to be the main cause of psoriasis a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described. Introduction Cytokines are intercellular signaling proteins that serve as key modulators of the immune system and inflammation. Cells respond to extracellular stress or stimuli by operating intracellular signaling cascades that coordinate .
