scholarly journals Anti-Inflammatory Activity of a Cyclic Tetrapeptide in Mouse and Human Experimental Models

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1030
Author(s):  
Michał Zimecki ◽  
Jolanta Artym ◽  
Wojciech Kałas ◽  
Leon Strządała ◽  
Katarzyna Kaleta-Kuratewicz ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Experimental Models ◽  
Toluene Diisocyanate ◽  
Peripheral Blood Mononuclear ◽  
Mouse Splenocytes ◽  
Anti Inflammatory ◽  
Cyclic Tetrapeptide

A cyclic tetrapeptide Pro-Pro-Pheβ3ho-Phe (4B8M) was tested for immunosuppressive activity and potential therapeutic utility in several in vitro and in vivo mouse and human models. The tetrapeptide was less toxic for mouse splenocytes in comparison to cyclosporine A (CsA) and a parent cyclolinopeptide (CLA). The tetrapeptide demonstrated potent anti-inflammatory properties in antigen-specific skin inflammatory reactions to oxazolone and toluene diisocyanate as well to nonspecific irritants such as salicylic acid. It also inhibited inflammatory processes in an air pouch induced by carrageenan. In addition, 4B8M proved effective in amelioration of animal models corresponding to human diseases, such as nonspecific colon inflammation induced by dextran sulfate and allergic pleurisy induced by ovalbumin (OVA) in sensitized mice. The tetrapeptide lowered expression of EP1 and EP3 but not EP2 and EP4 prostaglandin E2 (PGE2) receptors on lipopolysaccharide-stimulated Jurkat T cells and ICAM-1 expression on human peripheral blood mononuclear cells (PBMC). Its anti-inflammatory property in the carrageenan reaction was blocked by EP3 and EP4 antagonists. In addition, 4B8M induced an intracellular level of PGE2 in a human KERTr keratinocyte cell line. In conclusion, 4B8M is a low toxic and effective inhibitor of inflammatory disorders with potential therapeutic use, affecting the metabolism of prostanoid family molecules.

scholarly journals Anti-Inflammatory Activity of Fucoidan Extracts In Vitro

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 702
Author(s):  
Tauseef Ahmad ◽  
Mathew Suji Eapen ◽  
Muhammad Ishaq ◽  
Ah Young Park ◽  
Samuel S. Karpiniec ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Cytokine Production ◽  
Human Peripheral Blood ◽  
Laminaria Japonica ◽  
Macrocystis Pyrifera ◽  
Human Macrophage ◽  
Peripheral Blood Mononuclear ◽  
Anti Inflammatory

Fucoidans are sulfated, complex, fucose-rich polymers found in brown seaweeds. Fucoidans have been shown to have multiple bioactivities, including anti-inflammatory effects, and are known to inhibit inflammatory processes via a number of pathways such as selectin blockade and enzyme inhibition, and have demonstrated inhibition of inflammatory pathologies in vivo. In this current investigation, fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for modulation of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) by human peripheral blood mononuclear cells (PBMCs) and in a human macrophage line (THP-1). Fucoidan extracts exhibited no signs of cytotoxicity in THP-1 cells after incubation of 48 h. Additionally, all fucoidan extracts reduced cytokine production in LPS stimulated PBMCs and human THP-1 cells in a dose-dependent fashion. Notably, the 5–30 kDa subfraction from Macrocystis pyrifera was a highly effective inhibitor at lower concentrations. Fucoidan extracts from all species had significant anti-inflammatory effects, but the lowest molecular weight subfractions had maximal effects at low concentrations. These observations on various fucoidan extracts offer insight into strategies that improve their efficacy against inflammation-related pathology. Further studies should be conducted to elucidate the mechanism of action of these extracts.

scholarly journals Intrinsic Immunomodulatory Effects of Low-Digestible Carbohydrates Selectively Extend Their Anti-Inflammatory Prebiotic Potentials

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Jérôme Breton ◽  
Coline Plé ◽  
Laetitia Guerin-Deremaux ◽  
Bruno Pot ◽  
Catherine Lefranc-Millot ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Short Chain Fatty Acids ◽  
Trinitrobenzene Sulfonic Acid ◽  
Peripheral Blood Mononuclear ◽  
Fermentation Products ◽  
Anti Inflammatory ◽  
The Impact

The beneficial effects of carbohydrate-derived fibers are mainly attributed to modulation of the microbiota, increased colonic fermentation, and the production of short-chain fatty acids. We studied the direct immune responses to alimentary fibers inin vitroandin vivomodels. Firstly, we evaluated the immunomodulation induced by nine different types of low-digestible fibers on human peripheral blood mononuclear cells. None of the fibers tested induced cytokine production in baseline conditions. However, only one from all fibers almost completely inhibited the production of anti- and proinflammatory cytokines induced by bacteria. Secondly, the impact of short- (five days) and long-term (three weeks) oral treatments with selected fibers was assessed in the trinitrobenzene-sulfonic acid colitis model in mice. The immunosuppressive fiber significantly reduced levels of inflammatory markers over both treatment periods, whereas a nonimmunomodulatory fiber had no effect. The two fibers did not differ in terms of the observed fermentation products and colonic microbiota after three weeks of treatment, suggesting that the anti-inflammatory action was not related to prebiotic properties. Hence, we observed a direct effect of a specific fiber on the murine immune system. This intrinsic, fiber-dependent immunomodulatory potential may extend prebiotic-mediated protection in inflammatory bowel disease.

scholarly journals Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2516-2525 ◽  
Author(s):  
K Meszaros ◽  
S Aberle ◽  
R Dedrick ◽  
R Machovich ◽  
A Horwitz ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Binding Protein ◽  
Mononuclear Phagocytes ◽  
Factor Vii ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Fragment

Abstract Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia. In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades. In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity. We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (> or = 10 pg/mL). The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum. Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23. The expression of tumor necrosis factor showed qualitatively similar changes. Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.

Simvastatin Suppresses Interleukin Iβ Release in Human Peripheral Blood Mononuclear Cells Stimulated With Cholesterol Crystals

2018 ◽  
Vol 23 (6) ◽  
pp. 509-517 ◽  
Author(s):  
Anna J. Boland ◽  
Nisha Gangadharan ◽  
Pierce Kavanagh ◽  
Linda Hemeryck ◽  
Jennifer Kieran ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Nlrp3 Inflammasome ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Statins are mainstream therapy in the treatment and prevention of cardiovascular disease through inhibitory effects on cholesterol synthesis. However, statins’ beneficial effects in cardiovascular disease may also be attributable to their role as anti-inflammatory mediators. Here, we investigated the effects of simvastatin treatment on expression levels of interleukin (IL) 1β in both patient with hyperlipidemia and healthy human peripheral blood mononuclear cells (PBMCs) using cholesterol crystals (CC), a cardiovascular pathogenic stimulus for activation of the NOD-like receptor pyrin domain–containing protein 3 (NLRP3) inflammasome. Cholesterol crystal-induced NLRP3 inflammasome activation was used to trigger maturation and release of IL-1β in PBMCs. Specifically, isolated PBMCs from patients with hyperlipidemia at baseline and following 8 weeks of in vivo treatment with simvastatin (10-20 mg) daily were stimulated with lipopolysaccharide (LPS; 100 ng/mL) for 3 hours to induce proIL-Iβ expression followed by CC (2 mg/mL) stimulation for further 18 hours to activate the NLRP3 inflammasome complex to induce maturation/activation of IL-1β. Peripheral blood mononuclear cells were also isolated from healthy donors and stimulated in vitro with simvastatin (50, 25, 5, and 2 µmol/L) prior to stimulation with LPS and CC as described above. The effects of simvastatin treatment on levels of IL-1β expression were determined by enzyme-linked immunosorbent assay and western blot. Both in vitro and in vivo treatments with simvastatin led to a significant reduction in the levels of expression of IL-1β in response to stimulation with CC. Simvastatin inhibits the expression and activation of IL-1β induced by CC in PBMCs, which may contribute to its protective role in patients with cardiovascular disease.

Neopterin suppresses the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase in human peripheral blood mononuclear cells

Pteridines ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 237-243
Author(s):  
Sebastian Schroecksnadel ◽  
Elena-Sophia Ledjeff ◽  
Johanna Gostner ◽  
Christiana Winkler ◽  
Katharina Kurz ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Indoleamine 2,3 Dioxygenase ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

AbstractIn vitro, large amounts of neopterin are released from human monocyte-derived macrophages and dendritic cells primarily upon stimulation with Th1-type cytokine interferon-γ (IFN-γ). IFN-γ also induces the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) to form kynurenine (KYN). IDO-mediated TRP catabolism is very effective in suppressing the proliferation of T lymphocytes as well as of pathogens in vitro and in vivo. In this study, we investigated whether exogenously added neopterin may influence IDO activity in resting and in stimulated peripheral blood mononuclear cells (PBMC). PBMC were isolated from healthy donors, and neopterin was added in a concentration range from 0.01 to 50 μmol/L. After 30 min, PBMC were stimulated or not with 10 μg/mL of mitogen phytohemagglutinin (PHA). After 48 h, culture supernatants were collected, KYN and TRP concentrations were measured by high-performance liquid chromatography, and the ratio of KYN vs. TRP was calculated as an estimate of IDO activity. Spontaneous as well as PHA-induced TRP breakdown was suppressed by exogenously added neopterin in a dose-dependent way; the lowest active concentration of neopterin was <100 nmol/L. As neopterin concentrations in the nanomolar range are commonly observed in patients suffering from infections, sepsis, or uremia, our results suggest that neopterin formation might also serve as a feedback mechanism to slow down TRP degradation in vivo.

scholarly journals Inhibition of Fumarate Reductase inLeishmania major and L. donovani by Chalcones

2001 ◽  
Vol 45 (7) ◽  
pp. 2023-2029 ◽  
Author(s):  
Ming Chen ◽  
Lin Zhai ◽  
Søren Brøgger Christensen ◽  
Thor G. Theander ◽  
Arsalan Kharazmi
Keyword(s):  
Respiratory Chain ◽  
Mammalian Cells ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Fumarate Reductase ◽  
Peripheral Blood Mononuclear ◽  
Licochalcone A

ABSTRACT Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4′-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4′-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. majorpromastigotes. Although licochalcone A inhibited the activities of succinate dehydrogenase (SDH), NADH dehydrogenase (NDH), and succinate- and NADH-cytochrome c reductases in the parasite mitochondria, the 50% inhibitory concentrations (IC50) of licochalcone A for these enzymes were at least 20 times higher than that for FRD. The IC50 of licochalcone A for SDH and NDH in human peripheral blood mononuclear cells were at least 70 times higher than that for FRD. These findings indicate that FRD, one of the enzymes of the parasite respiratory chain, might be the specific target for the chalcones tested. Since FRD exists in the Leishmaniaparasite and does not exist in mammalian cells, it could be an excellent target for antiprotozoal drugs.

scholarly journals Promising Immunomodulatory Effects of Selected Strains of Dairy Propionibacteria as Evidenced In Vitro and In Vivo

2010 ◽  
Vol 76 (24) ◽  
pp. 8259-8264 ◽  
Author(s):  
Benoît Foligné ◽  
Stéphanie-Marie Deutsch ◽  
Jérôme Breton ◽  
Fabien J. Cousin ◽  
Joëlle Dewulf ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 10 ◽  
Peripheral Blood Mononuclear ◽  
Probiotic Potential ◽  
Dairy Propionibacteria ◽  
Strain Dependent ◽  
Anti Inflammatory Cytokine

ABSTRACT Immunomodulatory properties of 10 dairy propionibacteria, analyzed on human peripheral blood mononuclear cells (PBMCs), revealed a highly strain-dependent induction of anti-inflammatory cytokine interleukin 10 (IL-10). Two selected strains of Propionibacterium freudenreichii showed a protective effect against two models of colitis in mice, suggesting a probiotic potential predicted by immune-based selection criteria for these cheese starter bacteria.

scholarly journals Partial chemical and functional characterization of milk whey products obtained by different processes

2012 ◽  
Vol 32 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Fabiane La Flor Ziegler ◽  
Georgia Alvares Castro ◽  
Yara Maria Franco Moreno ◽  
Vanessa Oya ◽  
Maria Marluce dos Santos Vilela ◽  
...  
Keyword(s):  
Whey Protein ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Functional Characterization ◽  
Interleukin 4 ◽  
In Vivo Studies ◽  
Whey Protein Concentrate ◽  
Peripheral Blood Mononuclear

Whey protein samples (S-1 to S-5) were tested in vivo and in vitro for nutritional properties and selected bioactivities. Weanling male Wistar rats fed modified AIN-93G (12 g protein.100 g-1) diets for 21 days were used the in vivo studies. The nutritional parameters did not differ among the protein diets tested. Erythrocyte glutathione content was considered high and was higher for S-3, but liver glutathione was the same for all dietary groups. For S-3, cytokine secretion (IL-10 and TNF-α) by human peripheral blood mononuclear cells (in RPMI-1640 medium) was higher in the absence of antigen than in the presence of BCG antigen. Interleukin-4 secretion was repressed in all treatments. The IC50, whey protein concentration required to inhibit 50% of the melanoma cell proliferation, was 2.68 mg.mL-1 of culture medium for the S-3 sample and 3.66 mg.mL-1 for the S-2 sample. Based on these results, it was concluded that S-3 (whey protein concentrate enriched with TGF-β and lactoferrin) produced better nutritional and immunological responses than the other products tested.

High levels of thyroid hormone impair regulatory T cells function via reduced PD-1 expression

2021 ◽  
Author(s):  
Yi Zhong ◽  
Ting-Ting Lu ◽  
Xiao-Mei Liu ◽  
Bing-Li Liu ◽  
Yun Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Thyroid Hormone ◽  
Regulatory T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear

Abstract Context Regulatory T cells (Tregs) dysfunction plays an important role in the development and progression of Graves’ disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Tregs expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown of Tregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined. Objective To evaluate the role of PD-1 in Tregs function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3. Methods We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Tregs function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice with T3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo. Results PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulating T3 reduced PD-1 expression in Tregs, impaired Tregs function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3. Conclusions Tregs dysfunction in GD patients might be due to down-regulation of PD-1 expression in Tregs induced by high levels of serum T3.

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