Peptide Hp(2-20) accelerates healing of TNBS-induced colitis in the rat.

Background and aims: Hp(2-20), a Helicobacter pylori- derived peptide interacting with N-formyl peptide receptors (FPRs), accelerates the healing of gastric injury in rats. Whether Hp(2-20) affects the recovery of inflamed colonic mucosa is unknown. We evaluated whether Hp(2-20) accelerated the healing of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis and explored the mechanism(s) underlying any such effect.

Methods: Fifteen rats underwent rectal administration of Hp(2-20) 250-500 µg/kg/day, or of its control peptide Hp1 for 10 days, following induction of colitis with TNBS. Macroscopic and histological damage was quantified using predetermined injury scores. FPR1 , COX-2 , TNF-α , TGF-β , HB-EGF and tissue transglutaminase ( t-TG ) messenger RNA (mRNA) expression in colonic tissue was determined by quantitative polymerase chain reaction; FPR1, TNF-α and COX-2 protein levels by Western blotting.

Results: (1) Hp(2-20) accelerated healing of TNBS-induced colitis compared to controls consistently with the expression of FPRs in colonic mucosa; (2) TNBS upregulated mRNA mucosal expression of COX-2 , TNF-α , TGF-β , HB-EGF and t-TG and (3) this, with the exception of HB-EGF , was significantly counteracted by Hp(2-20).

Conclusions: Hp(2-20), an FPR agonist, accelerates the healing of TNBS-induced colitis in the rat. This effect is associated with a significant reduction in colonic tissue levels of COX-2 , TGF-β , TNF-α and t-TG . We postulate that FPR-dependent pathways may be involved in the repair of inflamed colonic mucosa.