ORIGINAL CONTRIBUTION Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils Marı ´a Edith Reyes-Quiroz • Gonzalo Alba • Javier Saenz • Consuelo Santa-Marı ´a • Isabel Geniz • Juan Jime ´nez • Remedios Ramı ´rez • Jose ´ Martı ´n-Nieto • Elizabeth Pintado • Francisco Sobrino Received: 19 September 2013 / Accepted: 19 February 2014 / Published online: 11 April 2014 Ó Springer-Verlag Berlin Heidelberg 2014 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 LXRa and LXRa-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 LXRa 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 rele- vant 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 lM 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 evi- dence 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 neu- trophils during inflammation. Keywords Oleic acid Á LXRa Á Transcriptional regulation Á Nutrition science Á Inflammation Á MAP kinases Introduction The fine regulation of the transcription of genes encoding liver X receptors (LXRs) a and b is an essential metabolic adaptation to fluctuations in cholesterol and lipid ingest. Dietary fatty acids (FAs) are a source of energy and structural components for cells, but also serve as mediators of signal transduction. FAs may regulate the activity and expression of transcription factors, including peroxisome proliferator-activated receptor (PPAR), hepatic nuclear factor (HNF-4), LXR and the sterol regulatory element- binding protein 1c (SREBP1c) [1]. LXRs are known to positively regulate the expression of genes involved in M. E. Reyes-Quiroz Á G. Alba Á J. Saenz Á J. Jime ´nez Á R. Ramı ´rez Á E. Pintado Á F. Sobrino (&) Departamento de Bioquı ´mica Me ´dica y Biologı ´a Molecular, Facultad de Medicina, Universidad de Sevilla, Avda. Sa ´nchez Pizjua ´n 4, 41009 Sevilla, Spain e-mail: fsobrino@us.es C. Santa-Marı ´a Departamento de Bioquı ´mica y Biologı ´a Molecular, Universidad de Sevilla, Sevilla, Spain I. Geniz Distrito Sanitario Sevilla Norte, Servicio Andaluz de Salud, Sevilla, Spain J. Martı ´n-Nieto Departamento de Fisiologı ´a, Gene ´tica y Microbiologı ´a, Universidad de Alicante, Alicante, Spain 123 Eur J Nutr (2014) 53:1707–1717 DOI 10.1007/s00394-014-0677-0