N-3 polyunsaturated fatty acids reduce allergic type mediator release by human mast cells in vitro via inhibition of reactive oxygen species

2011 ◽  
Vol 668 ◽  
pp. e33-e34
Author(s):  
L.W.J. van den Elsen⁎ ◽  
Y. Nusse ◽  
F.A. Redegeld ◽  
E.F. Knol ◽  
J. Garssen ◽  
...  
2012 ◽  
Vol 109 (10) ◽  
pp. 1821-1831 ◽  
Author(s):  
Lieke W. J. van den Elsen ◽  
Yvette Nusse ◽  
Martin Balvers ◽  
Frank A. Redegeld ◽  
Edward F. Knol ◽  
...  

Increased n-6 and reduced n-3 long-chain PUFA (LC-PUFA) intake in Western diets may contribute to the increased prevalence of allergic diseases. Key effector cells in allergy are mast cells (MC). The aim of the present study was to investigate the effects of n-6 v.n-3 LC-PUFA on MC phenotype. Human MC lines (LAD2 and HMC-1) were incubated for 24 h with either arachidonic acid (AA, n-6 LC-PUFA) or the n-3 LC-PUFA EPA or DHA. The effects of these three LC-PUFA on degranulation, mediator secretion and reactive oxygen species (ROS) generation were assessed. ROS, mitogen-activated protein kinase (MAPK) or NF-κB inhibitors were used to unravel signalling pathways involved in cytokine secretion. AA, EPA or DHA did not reduce IgE-mediated degranulation by LAD2 cells. However, AA increased PGD2 and TNF-α secretion by ionomycin/phorbol 12-myristate 13-acetate-stimulated HMC-1, whereas EPA and DHA more prominently inhibited IL-4 and IL-13 secretion. Suppression of IL-4 and IL-13 release by LC-PUFA correlated with reduced ROS generation. IL-4 and IL-13 release by activated HMC-1 was abrogated using ROS inhibitors. Inhibition of MAPK signalling, but not NF-κB, downstream of ROS reduced IL-13 secretion by activated HMC-1. Combined incubation of EPA or DHA with MAPK inhibitors further suppressed IL-13 secretion. In conclusion, the n-6 LC-PUFA AA enhanced pro-inflammatory mediator production by MC, while the n-3 LC-PUFA EPA as well as DHA more effectively suppressed ROS generation and IL-4 and IL-13 release. This suggests that dietary supplementation with EPA and/or DHA may alter the MC phenotype, contributing to a reduced susceptibility to develop and sustain allergic disease.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 388
Author(s):  
Xiao Dan Hui ◽  
Gang Wu ◽  
Duo Han ◽  
Xi Gong ◽  
Xi Yang Wu ◽  
...  

In this study, blueberry and blackcurrant powder were chosen as the phenolic-rich enrichments for oat bran. A Rapid Visco Analyser was used to form blueberry and blackcurrant enriched oat pastes. An in vitro digestion process evaluated the changes of phenolic compounds and the in vitro antioxidant potential of extracts of pastes. The anthocyanidin profiles in the extracts were characterised by the pH differential method. The results showed that blueberry and blackcurrant powder significantly increased the content of phenolic compounds and the in vitro antioxidant capacity of pastes, while the total flavonoid content decreased after digestion compared to the undigested samples. Strong correlations between these bioactive compounds and antioxidant values were observed. Lipopolysaccharide-stimulated RAW264.7 macrophages were used to investigate the intracellular antioxidant activity of the extracts from the digested oat bran paste with 25% enrichment of blueberry or blackcurrant powder. The results indicated that the extracts of digested pastes prevented the macrophages from experiencing lipopolysaccharide (LPS)-stimulated intracellular reactive oxygen species accumulation, mainly by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway. These findings suggest that the bioactive ingredients from blueberry and blackcurrant powder enhanced the in vitro and intracellular antioxidant capacity of oat bran pastes, and these enriched pastes have the potential to be utilised in the development of the functional foods.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhuochao Liu ◽  
Hongyi Wang ◽  
Chuanzhen Hu ◽  
Chuanlong Wu ◽  
Jun Wang ◽  
...  

AbstractIn this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.


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