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


RESULTS
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
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.
Cocco
Elisa
E
Department of Biology and Biotechnology Charles Darwin, Sapienza University, Rome, Italy.
Paladini
Fabiana
F
Macino
Giuseppe
G
Fulci
Valerio
V
Fiorillo
Maria Teresa
MT
Sorrentino
Rosa
R
D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015536:Down-Regulation / Q000235:genetics*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics*; D020298:U937 Cells; D015854:Up-Regulation / Q000276:immunology
D020413:3' Untranslated Regions; D008070:Lipopolysaccharides; D035683:MicroRNAs; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I