The expression of vasoactive intestinal peptide receptor 1 is negatively modulated by microRNA 525-5p.

E. Cocco (1) , F. Paladini (1) , G. Macino (1) , V. Fulci (1) , Mt Fiorillo (1) , R. Sorrentino (1)

1 UNIROMA1

BACKGROUND: The human Vasoactive Intestinal Peptide (VIP) is a neurokine with effects on the immune system where it is involved in promoting tolerance. In this context, one of its receptors, VPAC1, has been found to be down-modulated in cells of the immune network in response to activating stimuli. In particular, the bacterial liposaccharide (LPS), a strong activator of the innate immune system, induces a rapid decrease of VPAC1 expression in monocytes and this event correlates with polymorphisms in the 3'-UTR of the gene. METHODOLOGY/PRINCIPAL FINDINGS: MicroRNA 525-5p, having as putative target the 3'-UTR region of VPAC1, has been analysed for its expression in monocytes and for its role in down-modulating VPAC1 expression. We report here that miR-525-5p is promptly up-regulated in LPS-treated monocytes. This microRNA, when co-transfected in 293T cells together with a construct containing the 3'-UTR of the VPAC1 gene, significantly reduced the luciferase activity in a standard expression assay. The U937 cell line as well as primary monocytes enforced to express miR-525-5p, both down-modulate VPAC1 expression at similar extent. CONCLUSIONS/SIGNIFICANCE: Our results show that the response to an inflammatory stimulus elicits in monocytes a rapid increase of miR-525-5p that targets a signaling pathway involved in the control of the immune homeostasis.

Domaines: Immunologie

E. Cocco, F. Paladini, G. Macino, V. Fulci, Mt Fiorillo, et al.. The expression of vasoactive intestinal peptide receptor 1 is negatively modulated by microRNA 525-5p.. PLoS ONE, 2010, pp.e12067. ⟨hal-00543355⟩