title: Expression of microRNA-184 in keratinocytes represses argonaute 2.
abstract: Interleukin-22 (IL-22) is a proinflammatory cytokine that has been associated with the pathogenesis of inflammatory skin disorders. However, the impact of IL-22 on microRNA (miRNA) expression in epidermal keratinocytes is unknown. Here we show that IL-22 induces miR-184 in reconstituted human epidermis (RHE) and in the HaCaT keratinocyte cell line. Exposure to IL-22 increased miR-184 expression 8- and 15-fold in RHE and HaCaT cells, respectively. Oncostatin M, an unrelated proinflammatory cytokine, also raised miR-184 expression in RHE and HaCaT keratinocytes. Pharmacologic and genetic inhibition demonstrated that cytokine-induced expression of miR-184 was mediated by signal transducer and activation of transcription 3 (STAT3). Argonaute 2 (AGO2), a member of the RNA-induced silencing complex (RISC), is a predicted miR-184 target. Using protein, messenger RNA and reporter analyses, we found that miR-184 regulates the expression of AGO2. We conclude that cytokine-induced miR-184 attenuates AGO2 expression in keratinocytes.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Roberts
authors.forename: Richard B
authors.initials: RB
authors.lastname: Warren
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Kehinde
authors.initials: K
authors.lastname: Ross
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D060565:Argonaute Proteins; D007378:Interleukins; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C466422:AGO2 protein, human; C534424:MIRN184 microRNA, human; C494086:STAT3 protein, human