scholarly journals Stimulatory Response of Celiac Disease Peripheral Blood Mononuclear Cells Induced by RNAi Wheat Lines Differing in Grain Protein Composition

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2933 ◽  
Author(s):  
Susana Sánchez-León ◽  
María José Giménez ◽  
Isabel Comino ◽  
Carolina Sousa ◽  
Miguel Ángel López Casado ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Wheat Gluten ◽  
Protein Composition ◽  
Gluten Protein ◽  
Bread Making ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the diet. Interference RNA (RNAi) is an excellent approach for the down-regulation of genes coding for immunogenic proteins related to celiac disease, providing an alternative for the development of cereals suitable for CD patients. In the present work, we report a comparative study of the stimulatory capacity of seven low-gluten RNAi lines differing in grain gluten and non-gluten protein composition, relevant for CD and other gluten pathologies. Peripheral blood mononuclear cells (PBMCs) of 35 patients with active CD were included in this study to assess the stimulatory response induced by protein extracts from the RNAi lines. Analysis of the proliferative response and interferon-gamma (INF-γ) release of PBMCs demonstrated impaired stimulation in response to all RNAi lines. The lower response was provided by lines with a very low content of α- and γ-gliadins, and low or almost devoid of DQ2.5 and p31–43 α-gliadin epitopes. The non-gluten protein seems not to play a key role in PBMC stimulation.

scholarly journals Immunomodulatory and Antioxidant Properties of Wheat Gluten Protein Hydrolysates in Human Peripheral Blood Mononuclear Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1673 ◽  
Author(s):  
Ivan Cruz-Chamorro ◽  
Nuria Álvarez-Sánchez ◽  
Guillermo Santos-Sánchez ◽  
Justo Pedroche ◽  
María-Soledad Fernández-Pachón ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Biological Activities ◽  
Wheat Gluten ◽  
Protein Hydrolysates ◽  
Gluten Protein ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Peptides from several plant food proteins not only maintain the nutritional values of the original protein and decrease the environmental impact of animal agriculture, but also exert biological activities with significant health-beneficial effects. Wheat is the most important food grain source in the world. However, negative attention on wheat-based products has arose due to the role of gluten in celiac disease. A controlled enzymatic hydrolysis could reduce the antigenicity of wheat gluten protein hydrolysates (WGPHs). Therefore, the aims of the present study were to evaluate the effects of the in vitro administration of Alcalase-generated WGPHs on the immunological and antioxidant responses of human peripheral blood mononuclear cells (PBMCs) from 39 healthy subjects. WGPH treatment reduced cell proliferation and the production of the Type 1 T helper (Th1) and Th17 pro-inflammatory cytokines IFN-γ and IL-17, respectively. WPGHs also improved the cellular anti-inflammatory microenvironment, increasing Th2/Th1 and Th2/Th17 balances. Additionally, WGPHs improved global antioxidant capacity, increased levels of the reduced form of glutathione and reduced nitric oxide production. These findings, not previously reported, highlight the beneficial capacity of these vegetable protein hydrolysates, which might represent an effective alternative in functional food generation.

scholarly journals Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease

2015 ◽  
Vol 309 (11) ◽  
pp. G910-G917 ◽  
Author(s):  
Na Tian ◽  
Daniel A. Leffler ◽  
Ciaran P. Kelly ◽  
Joshua Hansen ◽  
Eric V. Marietta ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Mouse Model ◽  
Immune Responses ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Gliadin Antibodies ◽  
Blood Mononuclear Cells ◽  
Hla Dq2

Celiac disease (CD) is an inflammatory disorder triggered by ingested gluten, causing immune-mediated damage to the small-intestinal mucosa. Gluten proteins are strikingly similar in amino acid composition and sequence to proline-rich proteins (PRPs) in human saliva. On the basis of this feature and their shared destination in the gastrointestinal tract, we hypothesized that salivary PRPs may modulate gluten-mediated immune responses in CD. Parotid salivary secretions were collected from CD patients, refractory CD patients, non-CD patients with functional gastrointestinal complaints, and healthy controls. Structural similarities of PRPs with gluten were probed with anti-gliadin antibodies. Immune responses to PRPs were investigated toward CD patient-derived peripheral blood mononuclear cells and in a humanized transgenic HLA-DQ2/DQ8 mouse model for CD. Anti-gliadin antibodies weakly cross-reacted with the abundant salivary amylase but not with PRPs. Likewise, the R5 antibody, recognizing potential antigenic gluten epitopes, showed negligible reactivity to salivary proteins from all groups. Inflammatory responses in peripheral blood mononuclear cells were provoked by gliadins whereas responses to PRPs were similar to control levels, and PRPs did not compete with gliadins in immune stimulation. In vivo, PRP peptides were well tolerated and nonimmunogenic in the transgenic HLA-DQ2/DQ8 mouse model. Collectively, although structurally similar to dietary gluten, salivary PRPs were nonimmunogenic in CD patients and in a transgenic HLA-DQ2/DQ8 mouse model for CD. It is possible that salivary PRPs play a role in tolerance induction to gluten early in life. Deciphering the structural basis for the lack of immunogenicity of salivary PRPs may further our understanding of the toxicity of gluten.

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