Effects of Gliadin-Derived Peptides from Bread and Durum Wheats on Small Intestine Cultures from Rat Fetus and Coeliac Children

Auricchio, Salvatore; Ritis, G De; Vincenzi, Massimo De; Occorsio, P; Silano, Vittorio

doi:10.1203/00006450-198212000-00006

Cited by 98 publications

(57 citation statements)

References 5 publications

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“…Patchy slight degenerative changes were observed only in a few cultured jejunal from 10 fetuses. These findings confirm previous results by de Ritis et al (17) and Auricchio et al (4) showing that differentiation and maturation of small intestinal mucosa from rat fetuses takes place in vitro in a way comparable to in vivo differentiation.…”

Section: Resultssupporting

confidence: 82%

“…If the segments in the presence of barley peptides, and in 10 cultured results described in Table 1 are compared with those previously segments in the presence of sorghum prolamine peptides. Goblet reported by Auricchio et al (4) for PTC digests of bread wheat cells were absent in all the treated cultures. Last, in one culture gliadin, it is quite clear that no significant difference among toxicities of PTC digests of rye, oats, barley, sorghum, and bread wheat prolamines for culture of rat fetal intestine could be detected under our experimental conditions.…”

Section: Resultsmentioning

confidence: 95%

“…Prolamine fractions from the above cereals were obtained with an experimental procedure identical to that described by Auricchio et al (4) and summarized in Figure 1. Peptic-trypticCotazym digests of the purified prolamine fractions were prepared following the three-step procedure of Bronstein et al (1 1) as reported by de Ritis et al (17).…”

Section: Methodsmentioning

confidence: 99%

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An in Vitro Animal Model for the Study of Cereal Components Toxic in Celiac Disease

Auricchio¹,

Cardelli

Ritis³

et al. 1984

Pediatr Res

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ABSTRACT. Peptic-tryptic-Cotazym (PTC) digests were obtained, simulating in vivo protein digestion, from rice, maize, rye, oats, barley, and sorghum prolamines and tested on small intestine cultures from rat fetus. The PTC digests of the prolamine fractions from rice and maize, even when tested at a concentration as high as 0.5 mg/ml, did not affect in vitro differentiation and maturation of fetal rat jejunum that took place in vitro in a way comparable to what happens in vivo. On the contrary, the PTC digests of prolamines from rye, oats, barley, and sorghum were very active in slowing down in vitro development of fetal rat intestine. These results further strengthen earlier findings and all together show that there is a strong correlation between toxicity results of cereal and/or cereal components assessed with clinical trials or in vitro systems based on bioptic specimens of intestinal mucosa from celiac patients and with the culture of rat fetal intestine. Therefore, the rat fetal intestine culture is considered to be an adequate model for screening and investigating cereal peptides which are toxic for the celiac small intestinal mucosa. 18:1372-1378, 1984) Abbreviations PTC, peptic-tryptic-cotazym GP, gliadin peptides Celiac disease is an enteropathy occumng in genetically predisposed individuals (about 0.5/1000 of the general population) when wheat is a component of the diet. Under such circumstances, diarrhea and several malabsorption symptoms are observed in association with intestinal mucosa atrophy. Soon after the discovery that wheat is the environmental factor triggering the appearance of malabsorption symptoms, it was demonstrated that wheat toxicitv resulted from the gliadin protein fraction and that the other w h a t protein fractions, i.e. albumins, globulins, and glutenins, were harmless (6, 64, 65, 67). Later on it was shown (27, 28) that the ingestion of peptide mixtures obtained from wheat gluten after in vitro sequential digestion with proteolytic enzymes also induces the typical symptoms in patients affected by celiac disease. Moreover, clinical trials have shown Received July 29. 1983; February 7. 1984. Address correspondence to Salvatore Auricchio. Clinica Pediatrica, I1 Facolti di Medicina e Chirugia. Via Sergio Pansini 5 , 8013 1 Naples, Italy. This paper is dedicated by the authors to Professor Francesco Pocchiari on the occasion of his 60th birthday. (Pediatr Resthat, in addition to wheat, rye, barley, and probably oats also have toxicity (7, 41), whereas rice and maize are considered nontoxic and are usually used as wheat substitutes in the diet of celiac patients. It is presumed, but not demonstrated, that toxicity of cereals other than wheat is associated with prolamine fractions equivalent to gliadins in the grain of these other species.The detection and characterization of cereal components that are toxic in celiac disease are very difficult because no animal models exist for this disease. Falchuk et al. (19,20) have proposed the organ culture of human small intestinal biopsie...

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 95%

See 1 more Smart Citation

An in Vitro Animal Model for the Study of Cereal Components Toxic in Celiac Disease

Auricchio¹,

Cardelli

Ritis³

et al. 1984

Pediatr Res

Self Cite

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“…The fragments were placed on a stainless steel mesh positioned over the central well of an organ culture dish with the villous surface of the specimens uppermost. They were cultured for 24 h with medium alone, with the peptic-tryptic digest of gliadin from wheat bread (1 mg/ml), obtained as reported elsewhere (16), or with the peptic-tryptic digest of ovalbumin (1 mg/ml). The specimens were harvested, snap frozen in isopenthane, cooled in liquid nitrogen, and prepared for cryosectioning as described for immunohistochemistry.…”

Section: Methodsmentioning

confidence: 99%

In Vitro–Deranged Intestinal Immune Response to Gliadin in Type 1 Diabetes

Auricchio¹,

Paparo²,

Maglio³

et al. 2004

Diabetes

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Dietary gluten has been associated with an increased risk of type 1 diabetes. We have evaluated inflammation and the mucosal immune response to gliadin in the jejunum of patients with type 1 diabetes. Small intestinal biopsies from 17 children with type 1 diabetes without serological markers of celiac disease and from 50 age-matched control subjects were examined by immunohistochemistry. In addition, biopsies from 12 type 1 diabetic patients and 8 control subjects were cultured with gliadin or ovalbumin peptic-tryptic digest and examined for epithelial infiltration and lamina propria T-cell activation. The density of intraepithelial CD3 ؉ and ␥␦ ؉ cells and of lamina propria CD25 ؉ mononuclear cells was higher in jejunal biopsies from type 1 diabetic patients versus control subjects. In the patients' biopsies cultured with peptic-tryptic gliadin, there was epithelial infiltration by CD3 ؉ cells, a significant increase in lamina propria CD25 ؉ and CD80 ؉ cells and enhanced expression of lamina propria CD54 and crypt HLA-DR. No such phenomena were observed in control subjects, even those with celiac disease-associated HLA haplotypes. In conclusion, signs of mucosal inflammation were present in jejunal biopsies from type 1 diabetic patients, and organ culture studies indicate a deranged mucosal immune response to gliadin.

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“…Intriguingly, the presence of 10mer in the protein fraction of durum wheat could also account for the lower toxicity that gliadin peptides from durum wheat showed in small intestine cultures from celiac children (35). Recent articles pointed out that the lack of genome DD in durum wheat does not accounts by itself for lower toxicity of this grain in CD (36,37).…”

Section: Discussionmentioning

confidence: 99%

A Decapeptide from Durum Wheat Prevents Celiac Peripheral Blood Lymphocytes from Activation by Gliadin Peptides

Silano

Benedetto

Trecca³

et al. 2007

Pediatr Res

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ABSTRACT:Identifying antagonist peptides able to inhibit the abnormal immune response triggered by gliadin peptides in celiac disease (CD) is an alternative therapeutic strategy for CD. The aim of this study was to evaluate the antagonist effect of 10mer, a decapeptide (sequence QQPQDAVQPF) from alcohol-soluble protein fraction of durum wheat, assessing its ability to prevent celiac peripheral blood lymphocytes from activation by gliadin peptides. Peripheral blood mononuclear cells (PBMC) were obtained from DQ2-positive untreated coeliac children and from healthy controls and incubated with the peptic-tryptic digest of bread wheat gliadin (GLP) and peptide 62-75 from ␣-gliadin both alone and with 10mer simultaneously. PBMC proliferation, release of pro-inflammatory Th1 cytokines interferon-␥ and tumor necrosis factor-␣, release of immunoregulatory cytokine IL-10, and analysis of CD25 expression as indexes of lymphocytes activation were carried out. Enhanced lymphocytes activation was seen after exposure to GLP and p62-75, whereas the simultaneous incubation with 10mer inhibits the lymphocytes response. These data indicate that a peptide naturally occurring in durum wheat exerts in vitro an antagonist effect against gliadin toxicity and could have a protective effect in CD disease. C D is an increasingly diagnosed auto-immune enteropathy (prevalence 1:150), driven by an abnormal T-cell response to wheat gluten-derived peptides and strongly associated with HLA-DQ2, which is present in more than 90% of CD patients (1-3). So far, the only effective treatment is the withdrawal of the gluten-containing cereals from the diet (4). Complying with a gluten-free diet is difficult because of the diffusion of the cereals-based foods and it affects patients' quality of life; therefore, new treatments are being actively searched.An alternative therapeutic possibility may be to identify modified gliadin (a gluten fraction) peptides that are not toxic and are also able to inhibit the pathogenic immune response. In fact, some single amino acid substitutions at critical position of T-cell epitopes convert highly toxic peptides in ligand antagonists, as tested both in animal and ex vivo models (5,6). It has been reported that some peptides obtained by amino acid modifications of peptide 57-73 from ␣-gliadin abolish the production of interferon (IFN)-␥ by celiac PBMC incubated with the p57-73 itself (7).This therapeutic strategy could also rely upon ligand antagonists naturally occurring in some grains, such as a decapeptide (10mer) identified in the peptic-tryptic digest of the alcoholsoluble protein fraction of durum wheat (GLP) (8). This molecule, whose sequence is QQPQDAVQPF, named in previous studies "1157" after its molecular weight, has been demonstrated to protect some cellular lines from gliadin toxicity (8,9).Although in CD pathogenesis the central role is played by gluten-specific HLA DQ2/DQ8 restricted CD4ϩ intestinal T cells, recent studies indicate that the peripheral blood lymphocytes from celiac patients could be as ...

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Effects of Gliadin-Derived Peptides from Bread and Durum Wheats on Small Intestine Cultures from Rat Fetus and Coeliac Children

Cited by 98 publications

References 5 publications

An in Vitro Animal Model for the Study of Cereal Components Toxic in Celiac Disease

An in Vitro Animal Model for the Study of Cereal Components Toxic in Celiac Disease

In Vitro–Deranged Intestinal Immune Response to Gliadin in Type 1 Diabetes

A Decapeptide from Durum Wheat Prevents Celiac Peripheral Blood Lymphocytes from Activation by Gliadin Peptides

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