In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors

Jenny, M; Klieber, Martin; Zaknun, Daniela; Schroecksnadel, Sebastian; Kurz, Katharina; Ledochowski, Maximilian; Schennach, Harald; Fuchs, Dietmar

doi:10.1007/s00011-010-0244-y

Cited by 76 publications

(80 citation statements)

References 54 publications

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“…PBMCs were isolated from the peripheral blood of healthy human volunteers as described previously (Jenny et al, 2011) and collected in heparinized tubes. Separation of human PBMCs was performed using density centrifugation with Lymphoprep (Fresenius Kabi Norge AS, Oslo, Norway) (Dijkstra et al, 2007).…”

Section: Pbmc Isolationmentioning

confidence: 99%

Quercetin ameliorates LPS-induced inflammation in human peripheral blood mononuclear cells by inhibition of the TLR2-NF-κB pathway

Zhang

Lin

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Quercetin, a dietary flavonoid abundant in fruits, vegetables, and herbs, presents various pharmacological effects. This study aimed to investigate the anti-inflammatory effect and the underlying mechanism of quercetin in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs). Cell viability was measured by the Cell Counting Kit-8 assay. The mRNA expression of Toll-like receptor 2 (TLR2) was assessed by quantitative real-time polymerase chain reaction. Inflammatory cytokine secretions and nuclear factor (NF)-kB levels were analyzed by enzyme-linked immunosorbent assay. Our findings showed that quercetin significantly reduced LPS-induced cytotoxicity in human PBMCs. Quercetin suppressed the secretion of tumor necrosis factor-a, interleukin (IL)-1b, and IL-6 in LPS-stimulated human PBMCs. Moreover, quercetin reduced the LPS-induced increase in the expression of TLR2 mRNA and decreased the NF-kB concentration in LPS-stimulated human PBMCs. The data indicates that quercetin plays an important role in

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Section: Pbmc Isolationmentioning

confidence: 99%

Quercetin ameliorates LPS-induced inflammation in human peripheral blood mononuclear cells by inhibition of the TLR2-NF-κB pathway

Zhang

Lin

et al. 2016

Genet. Mol. Res.

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“…As Th1 and Th2 reactions crossregulate each other to balance immune responses [127] , suppression of Th1-type response by antioxidants would favour Th2-type reactions. Of note, several types of antioxidant were shown to reduce IFN-γ-stimulated tryptophan degradation and neopterin in peripheral blood mononuclear cells in vitro [87,128] . A number of studies reported an inverse relationship between plasma antioxidants, or total antioxidant capacity and cardiovascular diseases [5,15] .…”

Section: Antioxidants In Cvd Therapymentioning

confidence: 99%

Antioxidants, inflammation and cardiovascular disease

Mangge¹

2014

WJC

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Multiple factors are involved in the etiology of cardiovascular disease (CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells, leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species (ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or, and even more likely, due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress, however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover, molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signaling pathways involved in the regulation of immunological, metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response, interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase (IDO) in monocyte-derived macrophages, fibroblasts, endothelial and epithelial cells. Neopterin, a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase (NOS) is induced in several cell types to generate nitric oxide (NO). NO, despite its low reactivity, is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin (BH4), which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite (ONOO -) is formed solely in the presence of superoxide anion (O2 -). Neopterin and kynurenine to tryptophan ratio (Kyn/Trp), as an estimate of IDO enzyme activity, are robust markers of immune activation in vitro and in vivo . Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise, a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C, -E and -B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites, BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD. REVIEWSubmit a

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“…As a consequence of the suppressed Th1-type immunity and due to the cross-regulatory interaction between Th1-type and Th2-type immune responses [21,22], Th2-type cytokines are upregulated and the development of asthma and allergic diseases is favored [69]. Overall, one can summarize that oxidants and antioxidants are able to modulate the immune response [70,71,72]. Upon exposure to an allergen, Th2-type cytokines like IL-4, -10 and -13 are predominantly produced.…”

Section: Cross-regulation Of Th1- and Th2-type Immune Responsesmentioning

confidence: 99%

“…This conclusion is based on several in vitro studies which demonstrated that a variety of antioxidant compounds including vitamins C and E, as well as plant extracts and several common beverages with known antioxidative and anti-inflammatory properties, suppress the stimulation of peripheral blood mononuclear cells (PBMC), and this is reflected by a significant decline in neopterin production and tryptophan degradation in cells stimulated by mitogens [71,72] (table 1). The effects of antioxidant compounds were comparable to those observed earlier when effects of the Th2-type cytokine IL-4 or allergic mediators like histamine were investigated on stimulated PBMC and monocytic THP-1 cells [65,73], and they were also evident when the expression of NF-ĸB was monitored [55].…”

Section: Cross-regulation Of Th1- and Th2-type Immune Responsesmentioning

confidence: 99%

“…Among these agents there are not only vitamins, antioxidant phytochemicals, plant extracts and beverages, but also food preservatives like sodium sulfite, benzoate and sorbate as well as colorants like curcumin and beet root extract that are active in this way [71]. Moreover, in addition to slowing down the pathways related to Th1-type immunity in PBMC [74], vitamins C and E were also observed to induce the production of the Th2-type cytokine IL-4 and of IL-10 in a dendritic cell coculture system [75], and it was shown that the T cells expressed FoxP3 and, besides being anergic, might have acquired Treg properties.…”

Section: Cross-regulation Of Th1- and Th2-type Immune Responsesmentioning

confidence: 99%

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Potential Role of Antioxidant Food Supplements, Preservatives and Colorants in the Pathogenesis of Allergy and Asthma

Zaknun

Schroecksnadel²,

Kurz

et al. 2011

Int Arch Allergy Immunol

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A significant increase in the incidence of allergy and asthma has been observed during the past decades. The background of this phenomenon has not been well explained, but changes in lifestyle and habits are heavily discussed as contributing factors. Among these is a too clean environment, which may predispose individuals to increased sensitivity to allergic responses. Also the increase in dietary supplements including preservatives and colorants may contribute to this. In vitro, we and others have shown in freshly isolated human peripheral blood mononuclear cells that antioxidant compounds like vitamins C and E as well as food preservatives and colorants exert significant suppressive effects on the Th1 immune activation cascade. The effects observed may be based on the interaction of antioxidant compounds with proinflammatory cascades involving important signal transduction elements such as nuclear factor-ĸB. Although only obtained in vitro, these results show an anti-inflammatory property of compounds which could shift the Th1-Th2-type immune balance towards Th2-type immunity. This review article discusses the potential role of increased use of antioxidant food supplements as well as preservatives and colorants in the increase in allergy and asthma in the Western world.

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In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors

Cited by 76 publications

References 54 publications

Quercetin ameliorates LPS-induced inflammation in human peripheral blood mononuclear cells by inhibition of the TLR2-NF-κB pathway

Quercetin ameliorates LPS-induced inflammation in human peripheral blood mononuclear cells by inhibition of the TLR2-NF-κB pathway

Antioxidants, inflammation and cardiovascular disease

Potential Role of Antioxidant Food Supplements, Preservatives and Colorants in the Pathogenesis of Allergy and Asthma

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