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Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils

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Abstract

Purpose

Regulation of liver X receptors (LXRs) is essential for cholesterol homeostasis and inflammation. The present study was conducted to determine whether oleic acid (OA) could regulate mRNA expression of LXRα and LXRα-regulated genes and to assess the potential promotion of oxidative stress by OA in neutrophils.

Methods

Human neutrophils were treated with OA at different doses and LXR target gene expression, oxidative stress production, lipid efflux and inflammation state were analyzed.

Results

We describe that mRNA synthesis of both LXRα and ABCA1 (a reverse cholesterol transporter) was induced by OA in human neutrophils. This fatty acid enhanced the effects of LXR ligands on ABCA1 and LXR expression, but it decreased the mRNA levels of sterol regulatory element-binding protein 1c (a transcription factor that regulates the synthesis of triglycerides). Although OA elicited a slight oxidative stress in the short term (15–30 min) in neutrophils, it is unlikely that this is relevant for the modulation of transcription in our experimental conditions, which involve longer incubation time (i.e., 6 h). Of physiological importance is our finding that OA depresses intracellular lipid levels and that markers of inflammation, such as ERK1/2 and p38 mitogen-activated protein kinase phosphorylation, were decreased by OA treatment. In addition, 200 μM OA reduced the migration of human neutrophils, another marker of the inflammatory state. However, OA did not affect lipid peroxidation induced by pro-oxidant agents.

Conclusions

This work presents for the first time evidence that human neutrophils are highly sensitive to OA and provides novel data in support of a protective role of this monounsaturated acid against the activation of neutrophils during inflammation.

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Acknowledgments

We are indebted to Margarita Rodríguez Borrego for her technical assistance. M.E.R-Q was supported by a fellowship from the Asociación Virgen Macarena, Hospital Universitario Virgen Macarena, Sevilla. G.A. was supported by fellowships from the Ministerio de Educación y Ciencia (BFU2006-13802) and the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P08-CVI-03550). This work was funded by grants from the latter (P06-CTS-01936 and P08-CVI-03550) to F.S., and from the Consejería de Salud, Junta de Andalucía (CS 0116/2007) to E. P.

Conflict of interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán 4, 41009, Sevilla, Spain

    María Edith Reyes-Quiroz, Gonzalo Alba, Javier Saenz, Juan Jiménez, Remedios Ramírez, Elizabeth Pintado & Francisco Sobrino

  2. Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, Sevilla, Spain

    Consuelo Santa-María

  3. Distrito Sanitario Sevilla Norte, Servicio Andaluz de Salud, Sevilla, Spain

    Isabel Geniz

  4. Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain

    José Martín-Nieto

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  1. María Edith Reyes-Quiroz
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  2. Gonzalo Alba
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  3. Javier Saenz
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  9. Elizabeth Pintado
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  10. Francisco Sobrino
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Correspondence to Francisco Sobrino.

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Reyes-Quiroz, M.E., Alba, G., Saenz, J. et al. Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils. Eur J Nutr 53, 1707–1717 (2014). https://doi.org/10.1007/s00394-014-0677-0

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  • DOI: https://doi.org/10.1007/s00394-014-0677-0

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