Colon epithelial cellular protein induces oral tolerance in the experimental model of colitis by trinitrobenzene sulfonic acid.
Rectal administration of trinitrobenzene sulfonic acid (TNBS) produces chronic colitis in experimental animals. However, the role of epithelial cellular protein(s) in this model is unknown. We examined whether oral tolerance can be induced in this model with colon epithelial cell proteins and whether it is organ specific. Rats were fed five times with extracts of LS-180 human colon cancer cells or HT 1080 human fibroblast cells. Syngeneic normal rat colon or small intestinal extracts were fed to separate groups of rats. After oral feedings, each rat received TNBS by enema. Rats were killed 15 days later, and the following were measured: gross and histologic disease score, weight, thickness, and myeloperoxidase values of colon and serum interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) levels. Rectal TNBS alone produced severe colitis with a 26% mortality rate. Rats fed LS-180 or rat colon extract before TNBS enema were protected, as evidenced by reductions in mortality rate, disease scores, and myeloperoxidase values. However, rats fed HT 1080 or small intestine extract lacked such protection. To examine the possible mechanism of the oral tolerance, T lymphocytes from mesenteric lymph nodes and spleen of LS-180 extract-fed rats were passively transferred to naive rats, and this was followed by TNBS enema. These rats showed clear protection. Protected animals had low IFN-gamma and high TGF-beta levels. This study demonstrates that cellular protein(s) from human colon epithelial cells, but not from human fibroblasts, can induce oral tolerance in experimental colitis. This oral tolerance is mediated by primed mesenteric and splenic T lymphocytes.
Dasgupta
A
A
Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Department of Medicine, New Brunswick, NJ, USA.
Ramaswamy
K
K
Giraldo
J
J
Taniguchi
M
M
Amenta
P S
PS
Das
K M
KM
D000284:Administration, Oral; D000818:Animals; D002457:Cell Extracts / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000737:chemistry / Q000473:pathology; D003110:Colonic Neoplasms / Q000737:chemistry; D004848:Epithelium / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007108:Immune Tolerance; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000032:analysis; D007421:Intestine, Small / Q000737:chemistry; D008198:Lymph Nodes / Q000166:cytology; D009195:Peroxidase / Q000032:analysis; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum; D013154:Spleen / Q000166:cytology; D014020:Tissue Extracts / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000032:analysis; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D002457:Cell Extracts; D011506:Proteins; D014020:Tissue Extracts; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase