MicroRNAs modulate the noncanonical transcription factor NF-κB pathway by regulating expression of the kinase IKKα during macrophage differentiation

MicroRNAs are key regulators of many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation expression of the microRNAs miR-223 miR-15a and miR-16 decreased considerably which led to higher expression of the serine-threonine kinase IKK alpha in macrophages. In macrophages higher IKK alpha expression in conjunction with stabilization of the kinase NIK induced larger amounts of p52. Because of low expression of the transcription factor ReIB in untreated macrophages high p52 expression repressed basal transcription of both canonical and noncanonical NF-kappa B target genes. However proinflammatory stimuli in macrophages resulted in greater induction of noncanonical NF-kappa B target genes. Thus a decrease in certain microRNAs probably prevents macrophage hyperactivation yet primes the macrophage for certain responses to proinflammatory stimuli.