20 resultados para mononuclear cells


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Consumption of diets rich in monounsaturated fatty acids (MUFAs) has been linked with a low prevalence of atherosclerosis and there has been great interest in the effects of MUFAs on lipoprotein metabolism. Less attention has been paid to the effects of MUFAs on the immune system, yet cells of the immune system are an inherent part of the inflammatory events involved in atherosclerosis and several animal studies showed that olive oil has some potent immunomodulatory actions. We therefore considered it important to investigate the effects of chronic consumption of MUFAs on several immune cell functions in healthy humans. Healthy middle-aged males entered a doubleblind, randomized, controlled trial in which they consumed either a MUFA diet or a control diet for 2 mo. There was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells from subjects consuming the MUFA diet. Consumption of the MUFA diet did not affect natural killer cell activity or proliferation of mitogen-stimulated leukocytes. The effects of a MUFA-rich diet on adhesion molecule expression may have implications for the influence of dietary fat on inflammatory diseases, including atherosclerosis.

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Bifidobacterium longum bv. infantis CCUG 52486 was originally isolated from healthy elderly subjects and demonstrated to have particular ecological fitness and anti-pathogenic effects. Bifidobacteria are commonly associated with immunomodulatory properties, especially in older people, but this strain has not been investigated for effects on immune function. This study aimed to explore the immunomodulatory effects of this novel probiotic, compared with three commercial strains, B. longum SP 07/3, L. rhamnosus GG (L.GG) and L. casei Shirota (LcS). Human peripheral blood mononuclear cells (PBMCs) were isolated from fasting blood of young or older volunteers and exposed to probiotic strains or Con A. NK activity and activation, and cytokine release were enhanced by all probiotics with strain-specificities. The effect of B. infantis on NK activity was influenced by ageing. Except for L.GG, probiotics increased IFN-γ production to a much greater degree in young subjects, and increased IL-6 production to a much greater degree in older subjects. Based on IL-10/IL-12 ratios, B. infantis resulted in the most anti-inflammatory profile of all of the probiotics. These results suggest that B. infantis CCUG 52486 has strong immunomodulatory potential compared with well-known commercial strains, and that the immune response to probiotics may be influenced by ageing.

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Erythropoietic protoporphyria (EPP) is associated with a deficiency of protohaem ferrolyase. We have used a novel assay for this enzyme based on its ability to utilize zinc as a substrate to investigate the inheritance of EPP in nine affected families. Zinc chelatase activity was markedly reduced in peripheral blood mononuclear cells from 14 EPP patients (mean, 3.3 nmol Zn protohaem/h/mg protein; range, 0.3-8.0) when compared with 41 controls (16.8 +/- 3.6) p less than 0.01. In three families with parent-to-child transmission of disease, the asymptomatic parent had an enzymatic activity within the normal range. In three pedigrees where the parents were asymptomatic, enzymatic activities were below the 95% confidence limits in both. Zinc chelatase activity was below the mean control value in 17 of the 18 parents in nine affected pedigrees, and six of seven asymptomatic offspring of patients with protoporphyria. The findings suggest that EPP is not transmitted as a simple dominant trait and that inheritance of more than one gene may be required for disease expression.

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Natural plant-derived products are commonly applied to treat a broad range of human diseases, including cancer as well as chronic and acute airway inflammation. In this regard, the monoterpene oxide 1,8-cineol, the active ingredient of the clinically approved drug Soledum®, is well-established for the therapy of airway diseases, such as chronic sinusitis and bronchitis, chronic obstructive pulmonary disease and bronchial asthma. Although clinical trials underline the beneficial effects of 1,8-cineol in treating inflammatory diseases, the molecular mode of action still remains unclear. Here, we demonstrate for the first time a 1,8-cineol-depending reduction of NF-κB-activity in human cell lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS). Immunocytochemistry further revealed a reduced nuclear translocation of NF-κB p65, while qPCR and western blot analyses showed strongly attenuated expression of NF-κB target genes. Treatment with 1,8-cineol further led to increased protein levels of IκBα in an IKK-independent matter, while FRET-analyses showed restoring of LPS-associated loss of interaction between NF-κB p65 and IκBα. We likewise observed reduced amounts of phosphorylated c-Jun N-terminal kinase 1/2 protein in U373 cells after exposure to 1,8-cineol. In addition, 1,8-cineol led to decreased amount of nuclear NF-κB p65 and reduction of its target gene IκBα at protein level in human peripheral blood mononuclear cells. Our findings suggest a novel mode of action of 1,8-cineol through inhibition of nuclear NF-κB p65 translocation via IκBα resulting in decreased levels of proinflammatory NF-κB target genes and may therefore broaden the field of clinical application of this natural drug for treating inflammatory diseases.

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Abstract Background: Advancing age is linked to a decrease in beneficial bacteria such as Bifidobacterium spp. and reduced aspects of innate immune function. Objectives: We investigated whether daily consumption of a probiotic [Bacillus coagulans GBI-30, 6086 (BC30); GanedenBC30] could improve immune function and gut function in men and women aged 65–80 y, using a double-blind, placebo-controlled crossover design. Method: Thirty-six volunteers were recruited and randomly assigned to receive either a placebo (microcrystalline cellulose) or the probiotic BC30 (1 3 109 colony-forming units/capsule). Volunteers consumed 1 treatment capsule per day for 28 d, followed by a 21-d washout period before switching to the other treatment. Blood and fecal samples were collected at the beginning and end of each treatment period. Fecal samples were used to enumerate bacterial groups and concentrations of calprotectin. Peripheral blood mononuclear cells (PBMCs) were extracted from whole blood to assess natural killer cell activity and lipopolysaccharide (LPS)-stimulated cytokine production. C-reactive protein concentrations were measured in plasma. Results: Consumption of BC30 significantly increased populations of Faecalibacterium prausnitzii by 0.1 log10 cells/mL more than during consumption of the placebo (P = 0.03), whereas populations of Bacillus spp. increased significantly by 0.5 log10 cells/mL from baseline in volunteers who consumed BC30 (P = 0.007). LPS-stimulated PBMCs showed a 0.2 ng/mL increase in the anti-inflammatory cytokine IL-10 28 d after consumption of BC30 (P < 0.05), whereas the placebo did not affect IL-10, and no overall difference was found in the effect of the treatments. Conclusions: Daily consumption of BC30 by adults aged 65–80 y can increase beneficial groups of bacteria in the human gut and potentially increase production of anti-inflammatory cytokines. This study shows the potential benefits of a probiotic to improve dysbiosis via modulation of the microbiota in older persons. J Nutr doi: 10.3945/jn.114.199802.