In vitro activities of A-gliadin-related synthetic peptides: damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa.
BACKGROUND
Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH(2)-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has been investigated.


METHODS
Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought.


RESULTS
Peptides 31-55 and 31-43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25 positive cells.


CONCLUSIONS
Our results suggest that 31-43 and 44-55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.
Maiuri
L
L
Dept. of Pediatrics, University Federico II, Naples, Italy.
Troncone
R
R
Mayer
M
M
Coletta
S
S
Picarelli
A
A
De Vincenzi
M
M
Pavone
V
V
Auricchio
S
S
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology / Q000473:pathology*; D002648:Child; D000939:Epitopes / Q000276:immunology; D027261:Fusion Regulatory Protein-1; D005903:Gliadin / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D007583:Jejunum / Q000276:immunology / Q000378:metabolism; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000032:analysis
D015703:Antigens, CD; D002352:Carrier Proteins; D000939:Epitopes; D027261:Fusion Regulatory Protein-1; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D005903:Gliadin