LAUSR

Chronic skin inflammation in atopic eczema is associated with elevated expression of proinflammatory genes and activation of innate immune responses in keratinocytes. MicroRNAs (miRNAs) are short, single-stranded RNA molecules that silence genes via the degradation of target mRNAs or inhibition of translation. Recent studies have demonstrated that miR-124 is associated with regulation of inflammation factors in several diseases. The aim of this study was to investigate the role of miR-124 in skin inflammation of atopic eczema. We showed that miR-124 expression is decreased in chronic lesional skin of patients with atopic eczema, and could be strongly inhibited by IFN-γ and TNF-α. Through Western blot, real-time PCR and luciferase assays, we revealed that miR-124 inhibited the expression of p65, a member of NF-κB family which can regulate many factors involved in the immune response and inflammatory reactions, through direct targeting. Further, upon IFN-γ or TNF-α stimulation, IL8, CCL5 and CCL8 showed to be significantly upregulated by IFN-γ or TNF-α, downregulated by miR-124; the promotive effect of IFN-γ and TNF-α could be partially reversed by miR-124. The levels of IL8, CCL5 and CCL8 could be significantly downregulated by p65 knockdown, upregulated by miR-124 inhibition; the suppressive effect of p65 knockdown could be partially reversed by miR-124. Moreover, contrary to miR-124, p65, IL8, CCL5 and CCL8 mRNA expression was upregulated in chronic lesional skin of patients with atopic eczema, and all inversely correlated with miR-124. Taken together, our data demonstrate that miR-124 controls NF-κB-dependent inflammatory responses in keratinocytes and chronic skin inflammation in atopic eczema; rescuing miR-124 expression presents a promising strategy for atopic eczema treatment.