Antigen-Specific Gut Inflammation and Systemic Immune Responses Induced by Prolonging Wheat Gluten Sensitization in BALB/c Murine Model

• Published in: Journal of proteome research 2017-10, Vol.16 (10), p.3514-3528
• Main Authors: Vijaykrishnaraj, M, Mohan Kumar, B. V, Muthukumar, S. P, Kurrey, Nawneet K, Prabhasankar, P
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - blood; Antibodies - immunology; Antigens - immunology; Celiac Disease - blood; Celiac Disease - immunology; Celiac Disease - pathology; Disease Models, Animal; Gliadin - immunology; Glutens - adverse effects; Glutens - immunology; Humans; Immunity, Active; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Interleukins - genetics; Interleukins - immunology; Jejunum - drug effects; Jejunum - pathology; Lymphocytes - immunology; Lymphocytes - pathology; Mice; Triticum - adverse effects; Triticum - immunology; Wheat Hypersensitivity - blood; Wheat Hypersensitivity - immunology; Wheat Hypersensitivity - pathology
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.7b00199

Gluten-related diseases such as wheat allergy, celiac disease, and gluten intolerance are widespread around the globe to genetically predisposed individuals. The present study aims to develop a wheat-gluten induced BALB/c murine model for addressing wheat-gluten related disorders by sensitizing the wheat gluten through the route of intraperitoneal and oral challenge in prolonged days. During the sensitization, the sera were collected for specific antigliadin antibodies response and proinflammatory markers quantification. Ex vivo primary cells and organs were collected for subsequent analysis of inflammatory profile. Prolonging sensitization of gluten can moderate the antigen-specific inflammatory markers such as IL-1β, IL-4, IL-15, IL-6, IFN-γ and TNF-α levels in mice sera. However, ex vivo primary cells of splenocytes (SPLs) and intestinal epithelial lymphocytes (IELs) significantly increased the IL-6, IL-15, IL-1β, and IL-4 levels in G+ (gliadin and gluten) treated cells. Histopathology staining of jejunum sections indicates enterocyte degeneration in the apical part of villi and damage of tight junctions in G+ (gliadin and gluten) sensitized murine model. Immunohistochemistry of embedded jejunum sections showed significant expression of positive cells of IL-15, tTG and IL-4 in G+ sensitized murine model. In contrast, all markers of gluten-related disorders are expressed exclusively such as tTG, ZO-1, IL-15, IL-6, IL-4, and intestinal inflammation was mediated by iNOS, COX-2, TLR-4 and NF-kBp50 signaling mechanism in G+ sensitized mice.