scholarly journals Opposing Effects of Low Molecular Weight Heparins on the Release of Inflammatory Cytokines from Peripheral Blood Mononuclear Cells of Asthmatics

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0118798 ◽  
Author(s):  
Madhur D. Shastri ◽  
Niall Stewart ◽  
Mathew Eapen ◽  
Gregory M. Peterson ◽  
Syed Tabish R. Zaidi ◽  
...  
2007 ◽  
Vol 97 (05) ◽  
pp. 822-829 ◽  
Author(s):  
Peter Kierulf ◽  
Per Sandset ◽  
Olav Klingenberg ◽  
Gunn Joø ◽  
Hans Godal ◽  
...  

SummaryFibrinogen in plasma includes three main fractions; high-molecular- weight (HMW) -fibrinogen, low-molecular-weight (LMW) -fibrinogen, and very-low-molecular-weight (LMW`) -fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear.We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6,TNF- α and IL-1 β, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep® . HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF- α in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF- α concentrations were 12 (5, 40) pg/ ml and 16 (0,61) pg/ml,respectively.Median mRNA quantity was increased 12.3– (6.6, 48.6) and 1.7– (1.5, 6.5) fold for IL-6 and TNF- α compared to controls.The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC.The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.


2007 ◽  
Vol 75 (5) ◽  
pp. 2612-2620 ◽  
Author(s):  
Jyotsna Chandra ◽  
Thomas S. McCormick ◽  
Yoshifumi Imamura ◽  
Pranab K. Mukherjee ◽  
Mahmoud A. Ghannoum

ABSTRACT Monocytes and macrophages are the cell types most commonly associated with the innate immune response against Candida albicans infection. Interactions between the host immune system and Candida organisms have been investigated for planktonic Candida cells, but no studies have addressed these interactions in a biofilm environment. In this study, for the first time, we evaluated the ability of C. albicans to form biofilms in the presence or absence of adherent peripheral blood mononuclear cells (PBMCs; enriched for monocytes and macrophages by adherence). Our analyses using scanning electron and confocal scanning laser microscopy showed that the presence of PBMCs enhanced the ability of C. albicans to form biofilms and that the majority of PBMCs were localized to the basal and middle layers of the biofilm. In contrast to the interactions of PBMCs with planktonic C. albicans, where PBMCs phagocytose fungal cells, PBMCs did not appear to phagocytose fungal cells in biofilms. Furthermore, time-lapse laser microscopy revealed dynamic interactions between C. albicans and PBMCs in a biofilm. Additionally, we found that (i) only viable PBMCs influence Candida biofilm formation, (ii) cell surface components of PBMCs did not contribute to the enhancement of C. albicans biofilm, (iii) the biofilm-enhancing effect of PBMCs is mediated by a soluble factor released into the coculture medium of PBMCs with C. albicans, and (iv) supernatant collected from this coculture contained differential levels of pro- and anti-inflammatory cytokines. Our studies provide new insight into the interaction between Candida biofilm and host immune cells and demonstrate that immunocytes may influence the ability of C. albicans to form biofilms.


2009 ◽  
Vol 102 (2) ◽  
pp. 201-206 ◽  
Author(s):  
María Monagas ◽  
Nasiruddin Khan ◽  
Cristina Andrés-Lacueva ◽  
Mireia Urpí-Sardá ◽  
Mónica Vázquez-Agell ◽  
...  

Oligomers and polymers of flavan-3-ols (proanthocyanidins) are very abundant in the Mediterranean diet, but are poorly absorbed. However, when these polyphenols reach the colon, they are metabolised by the intestinal microbiota into various phenolic acids, including phenylpropionic, phenylacetic and benzoic acid derivatives. Since the biological properties of these metabolites are not completely known, in the present study, we investigated the effect of the following microbial phenolic metabolites: 3,4-dihydroxyphenylpropionic acid (3,4-DHPPA), 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid and 4-hydroxyhippuric acid (4-HHA), on modulation of the production of the main pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). The production of these cytokines by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) pre-treated with the phenolic metabolites was studied in six healthy volunteers. With the exception of 4-HHA for TNF-α secretion, only the dihydroxylated compounds, 3,4-DHPPA and 3,4-DHPAA, significantly inhibited the secretion of these pro-inflammatory cytokines in LPS-stimulated PBMC. Mean inhibition of the secretion of TNF-α by 3,4-DHPPA and 3,4-DHPAA was 84·9 and 86·4 %, respectively. The concentrations of IL-6 in the culture supernatant were reduced by 88·8 and 92·3 % with 3,4-DHPPA and 3,4-DHPAA pre-treatment, respectively. Finally, inhibition was slightly higher for IL-1β, 93·1 % by 3,4-DHPPA and 97·9 % by 3,4-DHPAA. These results indicate that dihydroxylated phenolic acids derived from microbial metabolism present marked anti-inflammatory properties, providing additional information about the health benefits of dietary polyphenols and their potential value as therapeutic agents.


2018 ◽  
Author(s):  
Ana Vitlic ◽  
Sohaib Sadiq ◽  
Hafiz I. Ahmed ◽  
Elisa C. Ale ◽  
Ana G. Binetti ◽  
...  

ABSTRACTLactobacillus fermentumLf 2 produces large amounts of exopolysaccharides under optimized conditions (∼2 g/L, EPS) which have been shown to possess immunomodulatory activity. In this study, the crude EPS was fractionated to give a high molecular weight (HMw) homoglycan and a mixture of medium molecular weight heteroglycans. The HMw EPS was isolated and identified as a β-glucan.Peripheral blood mononuclear cells (PBMC) were pre-treated with purified polysaccharide to determine if the HMw β-glucan is responsible for the immunomodulatory activity. Cells were also stimulated with either lipopolysaccharide (LPS) or phytohemagglutinin (PHA) and their effects, both with and without β-glucan pre-treatment, compared.Exposure of the cells to β-glucan increased their metabolic activity and whilst a small but statistically significant drop in CD14 expression was observed at Day 1, the levels were significantly elevated at Day 2. High levels of CD14 expression were observed in cells initially exposed to the β-glucan and subsequently stimulated with either LPS or PHA. In contrast, reduced levels of TLR-2 expression were observed for cells initially exposed to the β-glucan and subsequently stimulated with LPS.TNF-α levels were elevated in β-glucan treated cells (Day1) with the levels dropping back once the β-glucan had been removed (Day 2). The stimulants LPS and PHA both induced significant rises in TNF-α levels, however, this induction was completely (LPS) or partially blocked (PHA) in β-glucan pre-treated cells.The results indicate a role for the bacterial β-glucan in modulating the immune response following exposure to agonists such as bacterial LPS.


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