Platelet-activating factor and hydrogen peroxide exert a dual modulatory effect on the transcription of LXRα and its target genes in human neutrophils

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Título: Platelet-activating factor and hydrogen peroxide exert a dual modulatory effect on the transcription of LXRα and its target genes in human neutrophils
Autor/es: Reyes Quiroz, María Edith | Alba Jiménez, Gonzalo | Saenz, Javier | Geniz, Isabel | Jiménez Carrasco, Juan | Martín-Nieto, José | Santa María Pérez, Consuelo | Sobrino Beneyto, Francisco
Grupo/s de investigación o GITE: Genética Humana y de Mamíferos (GHM)
Centro, Departamento o Servicio: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Palabras clave: Liver X receptor | Human neutrophils, PAF | NF-κB | ERK1 and 2
Área/s de conocimiento: Genética
Fecha de publicación: sep-2016
Editor: Elsevier
Cita bibliográfica: International Immunopharmacology. 2016, 38: 357-366. doi:10.1016/j.intimp.2016.05.001
Resumen: Liver X receptors (LXRs) are ligand-activated nuclear receptors involved mainly in the regulation of cholesterol metabolism in many organs, including liver and intestine, as well as in macrophages and neutrophils. Besides, both anti-inflammatory and pro-inflammatory properties have been ascribed to LXRs. The effect of the inflammatory condition on the expression of LXRα and its target genes has not been previously addressed in human neutrophils. We have described that platelet-activating factor (PAF) and hydrogen peroxide (H2O2) are potent pro-inflammatory mediators that link the haemostatic and innate immune systems. In this work we report that H2O2 at low doses (1 pM-1 μM) exerts an inhibitory effect on TO901317-induced mRNA expression of LXRα and of its target genes encoding the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, and the sterol regulatory element-binding protein 1c (SREBP1c). However, an opposite behaviour, i.e., a transcription-enhancing effect, was found at higher H2O2 doses (100–500 μM) on most of these genes. A similar dual effect was observed when the pro-inflammatory molecule PAF was used. Interestingly, H2O2 production separately elicited by 10 nM PAF or 1 μM H2O2 was similarly low, and analogously, H2O2 production levels elicited by 5 μM PAF or 100 μM H2O2 were similarly high when they were compared. On the other hand, low doses of PAF or H2O2 induced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) and NF-κB activation, However, PAF or H2O2 at high doses did not produce changes in NF-κB activation levels. In summary, our results show that H2O2, either exogenous or PAF-induced, exerts a dual regulation on mRNA expression of LXRα and its target genes.
Patrocinador/es: 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.
ISSN: 1567-5769 (Print) | 1878-1705 (Online)
DOI: 10.1016/j.intimp.2016.05.001
Idioma: eng
Tipo: info:eu-repo/semantics/article
Derechos: © 2016 Published by Elsevier B.V.
Revisión científica: si
Versión del editor:
Aparece en las colecciones:INV - GHM - Artículos de Revistas

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