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P070. Healing of TNBS-induced colitis in the rat by peptide Hp(2-20)

M. Romano1, A.G. Gravina1, A. Federico1, G. D'Argenio2, C. Tuccillo1, A. Miranda1, N. Prevete3, A. De Paulis3, C. Loguercio1, 1Second University of Naples, Gastroenterology Unit, Department of Clinical and Experimental Medicine, Naples, Italy, 2Federico II University of Naples, Gastroenterology Unit, Department of Clinical and Experimental Medicine, Naples, Italy, 3Federico II University of Naples, Clinical Immunology and Allergy Division, Naples, Italy

Background

Hp(2-20) is a peptide derived from H. pylori ribosomal protein L1, which stimulates migration and proliferation of gastrointestinal epithelial cells by interacting with N-Formyl Peptide Receptors (N-FPRs), FPR-1 and FPR-2. We showed that Hp(2-20) accelerates healing of indomethacin-induced gastric injury in the rat. Whether Hp(2-20) is effective in the recovery of inflamed colonic mucosa is not known.

Methods

(1) 12 rats with TNBS-induced colitis (4 rats/group), underwent 10 days rectal administration of Hp(2-20) 250 mg or 500 mg/kg/day, or vehicle for Hp(2-20), starting 3 days after induction of colitis. (2) Macro- and microscopic damage was quantified using predetermined injury scores. (3) COX-2, TNF-alfa, TGF-beta, HB-EGF, tissue transglutaminase (t-TG), FPR-1 and FPR-2 mRNA colonic expression was determined by Real-Time PCR. (4) FPR-1 and FPR-2 mRNA expression was assessed in the colon of patients with ulcerative colitis in inflamed and healthy areas.

Results

(1) Hp(2-20) significantly (p < 0.05) improved the macroscopic and histological score of TNBS-induced colitis; (2) TNBS up-regulated mRNA levels of COX-2, TGF-beta, TNF-alfa, HB-EGF and t-TG in the colonic; (3) Hp(2-20) significantly (p < 0.05) decreased TNBS-induced mRNA overexpression of COX-2, TNF-beta, t-TG and TGF-alfa, whereas HB-EGF mRNA tissue levels remained unchanged; (4) TNBS up-regulated FPR-1 and FPR-2 mRNA expression and this was counteracted by Hp(2-20); (5) FPR-1 and FPR-2 mRNA expression was significantly up-regulated in the inflamed colon of patients with ulcerative colitis.

Conclusion

(1) Hp(2-20) accelerates mucosal healing in a rat model of TNBS colitis. (2) This effect is associated with a significant reduction in mRNA colonic tissue levels of COX-2, TGF-beta, TNF-alfa, and t-TG. (3) Hp(2-20) counteracted the increase in FPR-1 and FPR-2 mRNA expression induced by TNBS. (4) FPR-1 and FPR-2 mRNA expression is up-regulated in patients with ulcerative colitis. (5) We postulate that N-FPRs-dependent pathway may be involved in the repair of inflamed colonic mucosa and that Hp(2-20) may play a therapeutic role in inflammatory bowel diseases.