Open Access

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
  • View Affiliations

  • 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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May 2013
Volume 31 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Thulin P, Wei T, Werngren O, Cheung L, Fisher RM, Grandér D, Corcoran M and Ehrenborg E: MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response. Int J Mol Med 31: 1003-1010, 2013.
APA
Thulin, P., Wei, T., Werngren, O., Cheung, L., Fisher, R.M., Grandér, D. ... Ehrenborg, E. (2013). MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response. International Journal of Molecular Medicine, 31, 1003-1010. https://doi.org/10.3892/ijmm.2013.1311
MLA
Thulin, P., Wei, T., Werngren, O., Cheung, L., Fisher, R. M., Grandér, D., Corcoran, M., Ehrenborg, E."MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response". International Journal of Molecular Medicine 31.5 (2013): 1003-1010.
Chicago
Thulin, P., Wei, T., Werngren, O., Cheung, L., Fisher, R. M., Grandér, D., Corcoran, M., Ehrenborg, E."MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor δ in human monocytes during the inflammatory response". International Journal of Molecular Medicine 31, no. 5 (2013): 1003-1010. https://doi.org/10.3892/ijmm.2013.1311