Oral immunotherapy (OIT) is a promising therapeutic approach for treating food allergy. The treatment with heated ovomucoid-depleted egg white (HOMEW) in egg-allergic patients is noteworthy; however, ...OIT protocols are still experimental, and a better knowledge of the underlying mechanism is required. The objective of this work was to investigate the immunomodulatory effects of HOMEW and characterize the underlying mechanism in a BALB/c mouse model of egg allergy. Mice were sensitized with EW and treated with HOMEW. Post treatment, mice were challenged with EW and euthanized for collecting blood and spleen. Markers of allergic clinical outcomes were measured as histamine concentration, serum antibody activity, and cytokine production from cultured splenocytes. Digestibility of HOMEW was assessed mimicking physiological conditions in vitro. The HOMEW demonstrated high digestibility. The treatment induced a marked increase of the Th1/Th2 ratio in the high-dose treatment group. Treated mice had significantly less histamine, EW-specific IgE, and IL-4 and more IFN-γ and IL-10. This study confirms the mechanisms involved in successful tolerance induction with OIT using HOMEW and allows understanding of the vital role of surrogate allergy markers involved in immune modulation.
•Adenine inhibited tumor necrosis factor (TNF)-α secretion in RAW 264.7 cells.•The inhibition by adenine was significantly inhibited either AC or PKA inhibitors.•Adenine acts as an anti-endotoxin ...activity via a AdeR/AC/PKA signaling cascade.
It has previously demonstrated that adenine (6-amino-6H-purine) exhibited a vasoactive effect in contracted aorta. The adenine receptor (AdeR) has recently been identified as a G protein coupled purinergic receptor in diverse organs. It has been suggested that adenine acts as a signaling molecule through the activation of AdeR. The present study investigated the effect of adenine on endotoxin-stimulated mouse macrophages (RAW 264.7 cells) and focused on the AdeR signaling pathway. RAW 264.7 cells were treated with adenine and stimulated with lipopolysaccharide (LPS, Toll-like receptor 4 agonist) from Escherichia coli. Adenine inhibited tumor necrosis factor (TNF)-α secretion in RAW 264.7 cells. The inhibition by adenine was significantly attenuated in the presence of either adenyl cyclase (AC) or protein kinase A (PKA) inhibitors. Furthermore, adenine restored AdeR gene expression. These results firstly demonstrated that adenine acts as an anti-endotoxin compounds through a AdeR/AC/PKA signaling cascade.
•Eggshell membrane hydrolysate could protect cells from lipid and protein oxidation.•The peptides could up-regulate γ-glutamylcysteine synthetase activity.•The peptides could enhance several ...antioxidant enzyme activities in cells.•The peptides could be novel effective antioxidants against oxidative stress.
Excess reactive oxygen species (ROS) cause oxidative stress that is associated with the development of oxidative damage and chronic inflammation. The objective of this study was to evaluate the bioactivity of eggshell membrane (ESM) peptides digested with Alcalase and Protease S (AL-PS) at the cellular level. Effects were tested for inhibition of lipid and protein oxidation, synthesis of glutathione (GSH), and cellular antioxidant enzyme activity in H2O2-stimulated Caco-2 cells. AL-PS and its ultrafiltered fraction AL-PS-I (MWCO < 5 kDa) significantly suppressed the formation of H2O2-induced malondialdehyde (MDA) and protein carbonyl derivatives. AL-PS and AL-PS-I also increased glutathione peroxidase (GPx), glutathione S transferase (GST), and glutathione reductase (GR) activity. The peptides also elevated cellular GSH levels via up-regulation of γ-glutamylcysteine synthetase (γ-GCS) activity and its mRNA expression. This study confirms that ESM peptides are able to reduce intestinal oxidative stress and thus validates their use as a valuable source material of ESM waste.
Ovalbumin (OVA) is known as a major allergen in egg white. A number of studies have reported the partial T and B cell epitope mapping of OVA using murine models and allergic patients' sera. Recently, ...we have reported the IgE-binding regions of the entire OVA molecule using egg allergic patients' sera. However, the entire epitope mapping of OVA in a murine model has not been completed yet. In the present study, BALB/c mice were administered a solution of OVA using three different entry routes (oral, intraperitoneal and subcutaneous) with their respective adjuvant (cholera toxin, aluminum hydroxide and Freund's adjuvant). Two nitrocellulose membranes containing 188 overlapping synthetic peptides (with a length of 12 amino acids and an offset of two amino acids) covering the primary sequence of OVA, were probed with the three different BALB/c mice antisera. Antisera obtained from orally challenged mice identified eight IgE epitope regions, i.e. I53D60; V77R84; S103E108; G127T136; E275V280; G301F306; I323A332 and A375S384, while sera raised by intraperitoneal and subcutaneous injections exhibited two (K55D60 and K277L282) and five (K55R58; G127T136; K279L282; T303S308 and I323A332) IgE binding sequences, respectively. The residues critical for the epitope–paratope interactions were finely characterized using the oral immunization serum. Analysis of IgE binding epitopes in mice provides us with potential strategies for design of specific immunotherapy.
Tea, leaf, or bud from the plant Camellia sinensis, make up some of the beverages popularly consumed in different parts of the world as green tea, oolong tea, or black tea. More particularly, as a ...nonfermented tea, green tea has gained more renown because of the significant health benefits assigned to its rich content in polyphenols. As a main constituent, green tea polyphenols were documented for their antioxidant, anti-inflammation, anticancer, anticardiovascular, antimicrobial, antihyperglycemic, and antiobesity properties. Recent reports demonstrate that green tea may exert a positive effect on the reduction of medical chronic conditions such as cardiovascular disease, cancer, Alzheimer’s disease, Parkinson’s disease, and diabetes. The health benefits of green teas, in particular EGCG, are widely investigated, and these effects are known to be primarily associated with the structure and compositions of its polyphenols. This Review focuses on the diverse constituents of green tea polyphenols and their molecular mechanisms from the perspective of their potential therapeutic function. Recent advances of green tea polyphenols on their bioavailability, bioaccessibility, and microbiota were also summarized in this article. Dietary supplementation with green tea represents an attractive alternative toward promoting human health.
•HD-OVA and OVM demonstrated a skewed type 1 CD4+ T cell cytokine response.•HD-OVM inhibited intracellular Ca2+ concentration and decreased mast cell response.•Better understanding of the mechanisms ...behind induced tolerance of allergic individuals when consuming cooked egg.
The conformational epitopes of egg glycoproteins ovalbumin (OVA) and ovomucoid (OVM) recognized by IgE antibodies in an allergic response can be denatured at high temperatures. This structural change results in a decreased allergenicity and has earlier been used to induce clinical tolerance for specific oral immunotherapy in allergic patients via consumption of cooked egg products. We investigated the difference in allergic response when consuming heat-treated and native egg proteins by examining the cytokine production of CD4+ T cells and mast cell histamine release. Cultures of mouse CD4+ T cells and dendritic cells were stimulated with native and heat denatured OVA and OVM (HD-OVA and HD-OVM) and various cytokine and histamine concentrations were measured using ELISA. An increased concentration of IL-12, IL-17 and IL-10 and a decreased concentration of IL-4 were detected in both HD-OVA and HD-OVM (p < 0.05). A decreased concentration of histamine was detected in HD-OVM (p < 0.05) with human KU812 basophil like cells. Heat denatured egg proteins OVA and OVM demonstrated a skewed type 1 CD4+ T cell cytokine response and inhibited intracellular Ca2+ concentration. This study provides insights into understanding the mechanisms behind induced tolerance of allergic individuals when consuming cooked egg.
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•Heat-killed L. pentosus S-PT84 attenuates LPS-induced gut barrier dysfunction.•L. pentosus S-PT84 exhibits anti-inflammatory activity in the gut.•L. pentosus S-PT84 elevates ...adiponectin and reduces macrophage infiltration in white adipose tissue.•L. pentosus S-PT84 prevents dysbiosis in gut microbiota.
Chronic exposure to low-dose of endotoxin triggers a pronounced inflammatory responses impairing gut physical barrier and resulting in microbiota dysbiosis. In this study, we investigated the anti-inflammatory activity of dietary heat killed (HK) Lactobacillus pentosus S-PT84 in a lipopolysaccharides (LPS)-induced low-grade chronic inflammation C57BL/6J mouse model. The results showed that the deficient expression of tight junction proteins (ZO-1, Cldn 3 and JAMA) and mucin 2 were restored by HK L. pentosus S-PT84. Subsequently, HK L. pentosus S-PT84 attenuated the secretion of pro-inflammatory mediators (TNF-α and MCP-1) and the decreased levels of adiponectin with a reduction in macrophage infiltration in white adipose tissue (WAT). Moreover, the dysfunctional metabolic activity observed in WAT was significantly inhibited through upregulation of PPAR-γ and IRS-1 expression. The dysbiosis in gut microbiota were prevented by HK L. pentosus S-PT84. These findings suggest that HK L. pentosus S-PT84 exerts protective effects on intestinal mucosal integrity and an early risk for progression into metabolic disorders.
Obesity-induced adipose inflammation plays a crucial role in the development of obesity-induced metabolic disorders such as insulin resistance and type 2 diabetes. In the presence of obesity, ...hypertrophic adipocytes release inflammatory mediators, including tumor necrosis factor-alpha (TNFα) and monocyte chemoattractant protein-1 (MCP-1), which enhance the recruitment and activation of macrophages, and in turn augment adipose inflammation. We demonstrate that the soy peptide Phe-Leu-Val (FLV) reduces inflammatory responses and insulin resistance in mature adipocytes. Specifically, the soy peptide FLV inhibits the release of inflammatory cytokines (TNFα, MCP-1, and IL-6) from both TNFα-stimulated adipocytes and cocultured adipocytes/macrophages. This inhibition is mediated by the inactivation of the inflammatory signaling molecules c-Jun N-terminal kinase (JNK) and IκB kinase (IKK), and the downregulation of IκBα in the adipocytes. In addition, soy peptide FLV enhances insulin responsiveness and increases glucose uptake in adipocytes. More importantly, we, for the first time, found that adipocytes express peptide transporter 2 (PepT2) protein, and the beneficial action of the soy peptide FLV was disrupted by the peptide transporter inhibitor GlySar. These findings suggest that soy peptide FLV is transported into adipocytes by PepT2 and then downregulates TNFα-induced inflammatory signaling, thereby increasing insulin responsiveness in the cells. The soy peptide FLV, therefore, has the potential to prevent obesity-induced adipose inflammation and insulin resistance.
Calcium-sensing receptor (CaSR) is involved in maintaining cellular homeostasis and promoting recovery of damaged intestinal epithelial cells (IECs). Poly-l-lysine (PL) is a basic polypeptide ...identified for its role in the activation of CaSR through allosteric binding. The primary goal of the current study was to identify the modulatory effect of PL on intestinal inflammation and to determine whether these effects were mediated by CaSR activation. We used human intestinal epithelial cell lines, Caco-2 and HT-29, to assess PL anti-inflammatory activities in vitro. We found that PL reduced the IL-8 secretion from tumor necrosis factor (TNF)-α-treated human intestinal epithelial cell lines. On the other hand, the gene expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β was inhibited by PL supplementation. We subsequently evaluated the anti-inflammatory activity of PL in vivo using a DSS-induced mouse colitis model. PL supplementation was shown to prevent dextran sulfate sodium salt (DSS)-induced loss of weight, colitic symptoms, and shortening of colon length but maintained colonic morphology. The pro-inflammatory cytokine expression in the mouse colon, including TNF-α, IL-6, INF-γ, IL-17, and IL-1β, was significantly up-regulated by DSS treatment, but was inhibited upon PL administration. As shown by the results from both in vitro and in vivo studies, the reduction of inflammatory cytokine production caused by PL was reversed by NPS-2143 pretreatment. In the present study, we provide evidence that PL exerts anti-inflammatory effects on the gut system, which is primarily mediated by allosteric ligand activation of CaSR.
