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

Abstract

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 liposaccaride (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 39-UTR of the gene. Methodology/Principal Findings: MicroRNA 525-5p, having as putative target the 39-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 39-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. Citation: Cocco E, Paladini F, Macino G, Fulci V, Fiorillo MT, et al. (2010) The Expression of Vasoactive Intestinal Peptide Receptor 1 Is Negatively Modulated by MicroRNA 525-5p. PLoS ONE 5(8): e12067. doi:10.1371/journal.pone.0012067 Editor: Ralph Tripp, University of Georgia, United States of America Received April 8, 2010; Accepted July 14, 2010; Published August 10, 2010 Copyright:  2010 Cocco et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was partially supported by Istituto Pasteur-Fondazione Cenci-Bolognetti, Sapienza, University of Rome, Italy and by Volkswagen Stingtuf Foundation, Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: rosa.sorrentino@uniroma1.it . These authors contributed equally to this work.

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