To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.

• MeSH
• aktivace makrofágů imunologie   MeSH
• antigen CD83 MeSH
• antigeny CD40 metabolismus   MeSH
• antigeny CD80 metabolismus   MeSH
• antigeny CD86 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• celiakie imunologie   metabolismus   MeSH
• cytokiny biosyntéza   MeSH
• gliadin metabolismus   MeSH
• HLA-DQ antigeny metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• interleukin-8 biosyntéza   MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• monocyty metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• peptidové fragmenty MeSH
• průtoková cytometrie MeSH
• TNF-alfa biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• antigeny CD40 MeSH
• antigeny CD80 MeSH
• antigeny CD86 MeSH
• CD antigeny MeSH
• cytokiny MeSH
• gliadin MeSH
• HLA-DQ antigeny MeSH
• HLA-DQ2 antigen MeSH Prohlížeč
• imunoglobuliny MeSH
• interleukin-8 MeSH
• membránové glykoproteiny MeSH
• NF-kappa B MeSH
• peptidové fragmenty MeSH
• TNF-alfa MeSH

BACKGROUND: Sera of patients with coeliac disease, containing IgA and IgG antigliadin antibodies (AGA) and various IgA autoantibodies, react with isolated enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin. AIMS: To characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease. METHODS: AGA were isolated from sera of nine patients by affinity chromatography and tested by competitive ELISA using 40 alpha-gliadin synthetic dodecapeptides (A1-F6). RESULTS: Reactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central region; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1-D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes AGA of coeliac patients recognise similar structures corresponding to peptides A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Substitution of glutamine in the A4 peptide by glutamic acid caused loss of inhibitory capacity. Shortening of peptide A4 on the N-terminal by three amino acids increased its inhibitory effect. CONCLUSIONS: AGA of patients with coeliac disease react with similar structures on gliadin and potential autoantigens on enterocytes.

• MeSH
• autoantigeny imunologie   MeSH
• autoimunitní nemoci imunologie   MeSH
• celiakie imunologie   MeSH
• chromatografie afinitní MeSH
• dospělí MeSH
• ELISA MeSH
• epitopy analýza   MeSH
• gliadin chemie   imunologie   MeSH
• kalretikulin MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• peptidové fragmenty imunologie   MeSH
• potkani Wistar MeSH
• proteiny vázající vápník imunologie   MeSH
• protilátky krev   MeSH
• ribonukleoproteiny imunologie   MeSH
• střeva imunologie   MeSH
• zkřížené reakce MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• epitopy MeSH
• gliadin MeSH
• kalretikulin MeSH
• peptidové fragmenty MeSH
• proteiny vázající vápník MeSH
• protilátky MeSH
• ribonukleoproteiny MeSH

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.

• MeSH
• autoimunita imunologie   MeSH
• autoimunitní nemoci etiologie   imunologie   MeSH
• infekce imunologie   MeSH
• lidé MeSH
• myši MeSH
• střevní sliznice imunologie   mikrobiologie   MeSH
• syndromy imunologické nedostatečnosti imunologie   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Monoclonal, hyperimmune rabbit and human serum anti-gliadin antibodies were analyzed by ELISA and immunoblotting techniques. In Western blotting the difference in reactivity between monoclonal and human antibodies was quantitative rather than qualitative. Rabbit antisera differed in reactivity according to the protein used for immunization. The rabbits immunized by the peptic-tryptic pancreatic digest of gliadin reacted similarly to the patients. In ELISA, significantly higher reactivity with crude, A-, glyc-gli, alpha-, beta- and omega-gliadins was found in the patients' sera than in controls.

• MeSH
• antisérum imunologie   MeSH
• ELISA MeSH
• gliadin imunologie   MeSH
• imunizace metody   MeSH
• králíci imunologie   MeSH
• lidé MeSH
• monoklonální protilátky imunologie   izolace a purifikace   MeSH
• myši imunologie   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• králíci imunologie   MeSH
• lidé MeSH
• myši imunologie   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antisérum MeSH
• gliadin MeSH
• monoklonální protilátky MeSH

Mucosal surfaces covered by a layer of epithelial cells represent the largest and most critical interface between the organism and its environment. The barrier function of mucosal surfaces is performed by the epithelial layer and immune cells present in the mucosal compartment. As recently found, epithelial cells, apart from their participation in absorptive, digestive and secretory processes perform more than a passive barrier function and are directly involved in immune processes. Besides the well known role of epithelial cells in the transfer of polymeric immunoglobulins produced by lamina propria B lymphocytes to the luminal content of mucosals (secretory Igs), these cells were found to perform various other immunological functions, to interact with other cells of the immune system and to induce an efficient inflammatory response to microbial invasion: enzymic processing of dietary antigens, expression of class I and II MHC antigens, presentation of antigens to lymphocytes, expression of adhesive molecules mediating interaction with intraepithelial lymphocytes and components of extracellular matrix, production of cytokines and probable participation in extrathymic T cell development of intraepithelial lymphocytes. All these functions were suggested to influence substantially the mucosal immune system and its response. Under immunopathological conditions, e.g. during infections and inflammatory bowel and celiac diseases, both epithelial cells and intraepithelial lymphocytes participate substantially in inflammatory reactions. Moreover, enterocytes could become a target of mucosal immune factors. Mucosal immunosurveillance function is of crucial importance in various pathological conditions but especially in the case of the most frequent malignity occurring in the intestinal compartment, i.e. colorectal carcinoma. Proper understanding of the differentiation processes and functions of epithelial cells in interaction with other components of the mucosal immune system is therefore highly desirable.

• MeSH
• autoimunitní nemoci imunologie   patologie   MeSH
• Bacteria imunologie   MeSH
• celiakie imunologie   patologie   MeSH
• cytokiny fyziologie   MeSH
• dospělí MeSH
• epitel imunologie   MeSH
• epitelové buňky MeSH
• houby imunologie   MeSH
• idiopatické střevní záněty imunologie   patologie   MeSH
• imunoglobuliny imunologie   MeSH
• integriny fyziologie   MeSH
• kolorektální nádory imunologie   patologie   MeSH
• lidé MeSH
• lymfoidní tkáň cytologie   imunologie   MeSH
• membránové glykoproteiny fyziologie   MeSH
• myši knockoutované MeSH
• myši MeSH
• Peyerovy pláty imunologie   MeSH
• prezentace antigenu MeSH
• střeva mikrobiologie   MeSH
• střevní sliznice cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• imunoglobuliny MeSH
• integriny MeSH
• membránové glykoproteiny MeSH