Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro
Dias IH, Chapple IL, Milward M, Grant MM, Hill E, Brown J, Griffiths HR
PloS one · 66 citas
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Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Dunhill Medical Trust
- Organización sin fines de lucro
- Vivensa Foundation
- Subvenciones
- Dunhill Medical Trust (R92/1108)
Según 2 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2013-06-24 · PLoS One · vol. 8 · número 6 · pág. e66407
- Editorial
- Public Library of Science
- Citado
- 88 citas · más que el 94% de estudios similares · 4.0× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 58 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms · Immune Response and Inflammation · Adenosine and Purinergic Signaling
- Palabras clave
- GCLC, Glutathione, GCLM, Reactive oxygen species, Glutathione disulfide, NADPH oxidase, Oxidative stress, Chemistry, Nicotinamide adenine dinucleotide phosphate, Immunology, Internal medicine, Biochemistry, Biology, Oxidase test, Medicine
- MeSH
- neutrophils, hl-60 cells, humans, periodontitis, chronic disease, tetradecanoylphorbol acetate, isothiocyanates, sulfoxides, glutathione, respiratory burst, adult, middle aged, female, male, nf-e2-related factor 2, in vitro techniques, nadph oxidases
7 autores
- Irundika H.K. Dias🇬🇧Aston University
- Iain Chapple🇬🇧University of Birmingham
- Mike R. Milward🇬🇧University of Birmingham
- Melissa M. Grant🇬🇧University of Birmingham
- Eric James Hill🇬🇧Aston University
- James E. P. Brown🇬🇧Aston University
- Helen R. Griffiths🇬🇧 · autor de correspondenciaAston University
Resumen
El texto original del estudio, en el idioma en que se publicó.
The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. -) by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. -) production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.
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