MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response

Thulin,Petra; Wei,Tianling; Werngren,Olivera; Cheung,Louisa; Fisher,Rachel  M.; Grandér,Dan; Corcoran,Martin; Ehrenborg,Ewa

doi:10.3892/ijmm.2013.1311

MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response

Authors:
- Petra Thulin
- Tianling Wei
- Olivera Werngren
- Louisa Cheung
- Rachel M. Fisher
- Dan Grandér
- Martin Corcoran
- Ewa Ehrenborg
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Affiliations: Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital L8:03, SE-171 76 Stockholm, Sweden, Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Karolinska University Hospital R8:03, SE-171 76 Stockholm, Sweden
Published online on: March 20, 2013 https://doi.org/10.3892/ijmm.2013.1311
Pages: 1003-1010
Copyright: © Thulin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

PPARδ is involved in the inflammatory response and its expression is induced by cytokines, however, limited knowledge has been produced regarding its regulation. Since recent findings have shown that microRNAs, which are small non-coding RNAs that regulate gene expression, are involved in the immune response, we set out to investigate whether PPARδ can be regulated by microRNAs expressed in monocytes. Bioinformatic analysis identified a putative miR-9 target site within the 3'-UTR of PPARδ that was subsequently verified to be functional using reporter constructs. Primary human monocytes stimulated with LPS showed a downregulation of PPARδ and its target genes after 4 h while the expression of miR-9 was induced. Analysis of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages showed that human PPARδ mRNA as well as miR-9 expression was higher in M1 compared to M2 macrophages. Furthermore, treatment with the PPARδ agonist, GW501516, induced the expression of PPARδ target genes in the pro-inflammatory M1 macrophages while no change was observed in the anti-inflammatory M2 macrophages. Taken together, these data suggest that PPARδ is regulated by miR-9 in monocytes and that activation of PPARδ may be of importance in M1 pro-inflammatory but not in M2 anti-inflammatory macrophages in humans.

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