miR482f and miR482c-5p from edible plant-derived foods inhibit the expression of pro-inflammatory genes in human THP-1 macrophages

Ester Díez-Sainz; Silvia Lorente-Cebrián; Paula Aranaz; Ez-Zoubir Amri; José I Riezu-Boj; Fermín I Milagro

doi:10.3389/fnut.2023.1287312

miR482f and miR482c-5p from edible plant-derived foods inhibit the expression of pro-inflammatory genes in human THP-1 macrophages

Front Nutr. 2023 Nov 30:10:1287312. doi: 10.3389/fnut.2023.1287312. eCollection 2023.

Authors

Ester Díez-Sainz¹, Silvia Lorente-Cebrián^{2

3

4}, Paula Aranaz^{1

5}, Ez-Zoubir Amri⁶, José I Riezu-Boj^{1

5}, Fermín I Milagro^{1

5

7}

Affiliations

¹ Department of Nutrition, Food Science and Physiology/Center for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.
² Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Health and Sport Science, University of Zaragoza, Zaragoza, Spain.
³ Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
⁴ Aragón Health Research Institute (IIS-Aragon), Zaragoza, Spain.
⁵ Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
⁶ CNRS, Inserm, iBV, Université Côte d'Azur, Nice, France.
⁷ Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.

Abstract

Background: Edible plants can exert anti-inflammatory activities in humans, being potentially useful in the treatment of inflammatory diseases. Plant-derived microRNAs have emerged as cross-kingdom gene expression regulators and could act as bioactive molecules involved in the beneficial effects of some edible plants. We investigated the role of edible plant-derived microRNAs in the modulation of pro-inflammatory human genes.

Methods: MicroRNAs from plant-derived foods were identified by next-generation sequencing. MicroRNAs with inflammatory putative targets were selected, after performing in silico analyses. The expression of candidate plant-derived miRNAs was analyzed by qPCR in edible plant-derived foods and their effects were evaluated in THP-1 monocytes differentiated to macrophages. The bioavailability of candidate plant miRNAs in humans was evaluated in feces and serum samples by qPCR.

Results: miR482f and miR482c-5p are present in several edible plant-derived foods, such as fruits, vegetables, and cooked legumes and cereals, and fats and oils. Transfections with miR482f and miR482c-5p mimics decreased the gene expression of CLEC7A and NFAM1, and TRL6, respectively, in human THP-1 monocytes differentiated to macrophages, which had an impact on gene expression profile of inflammatory biomarkers. Both microRNAs (miR482f and miR482c-5p) resisted degradation during digestion and were detected in human feces, although not in serum.

Conclusion: Our findings suggest that miR482f and miR482c-5p can promote an anti-inflammatory gene expression profile in human macrophages in vitro and their bioavailability in humans can be achieved through diet, but eventually restricted at the gut level.

Keywords: CLEC7A; NFAM1; TLR6; cross-kingdom regulation; diet; inflammation; microRNA; xenomiRs.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn, grant No. CB12/03/30002), Ministerio de Asuntos Económicos y Transformación Digital (PID2022-141766OB-I00, RTI2018-102205-B-I00, and BFU2015-65937-R projects), and a Center for Nutrition Research pre-doctoral grant awarded to ED-S.