Regulation of pro-inflammatory cytokines TNF[alpha] and IL24 by microRNA-203 in primary keratinocytes

Cutaneous homeostasis and innate immunity is procured by a complex circuitry of intercellular cytokine signaling. MicroRNAs are important posttranscriptional regulators of keratinocyte gene expression and assist in modulating the fine balance between cell proliferation and differentiation in skin. A...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 2012-12, Vol.60 (3), p.741-748
Main Authors: Primo, Maria Nascimento, Bak, Rasmus O, Schibler, Beatrice, Mikkelsen, Jacob Giehm
Format: Article
Language:English
Subjects:
Cell proliferation
Cytokines
Differentiation
Gene expression
Homeostasis
Immune response
Immunity
Inflammation
Interleukin 24
Keratinocytes
miRNA
Mutagenesis
Post-transcription
Psoriasis
Skin
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Summary:Cutaneous homeostasis and innate immunity is procured by a complex circuitry of intercellular cytokine signaling. MicroRNAs are important posttranscriptional regulators of keratinocyte gene expression and assist in modulating the fine balance between cell proliferation and differentiation in skin. A characteristic microRNA profile in inflammatory skin suggests putative functions of microRNAs in perturbed cytokine production and signaling during chronic inflammatory skin conditions such as psoriasis. It remains unclear, however, why certain microRNAs are aberrantly expressed during skin inflammation and if they serve pro- and/or anti-inflammatory functions. In this report, we focus on cytokine regulation by microRNA-203 (miR-203), which is highly abundant in keratinocytes and upregulated in psoriatic lesions. By screening a panel of cytokines that are upregulated in psoriatic skin for regulation by miR-203, we identify the genes encoding the pro-inflammatory cytokines TNF[alpha] and IL24 as direct targets of miR-203. Studies of miR-203 overexpression, inhibition, and mutagenesis validate posttranscriptional regulation of TNF[alpha] and IL24 by miR-203 in cell lines and primary keratinocytes. Our findings suggest that miR-203 serves to fine-tune cytokine signaling and may dampen skin immune responses by repressing key pro-inflammatory cytokines.
ISSN:1043-4666
DOI:10.1016/j.cyto.2012.07.031