The migration of inflammatory cells to the sites of inflammation relies on the coordinated action of chemokines receptors (CXCRs) present on the inflammatory cells and chemotactic proteins produced at the site of inflammation. CXCR1 and CXCR2 are the CXCRs present on neutrophils and recognize CXCL8/IL-8 and are responsible for neutrophil infiltration at sites of inflammation. Recently, a collagen-breakdown product, Proline-Glycine-Proline (PGP) was shown to induce the infiltration of neutrophils via CXCR1 and CXCR2 in several lung diseases. PGP is formed from collagen by a combinational action of matrix metalloproteinase-9(MMP-9) and prolyl endopeptidase(PE), enzymes often found at sites of inflammation. To this end, we investigated the expression of both proteases in inflammatory bowel diseases (IBD). PE, large amount of MMP-9, as well as PGP were found in inflamed bowel tissue. Both MMP9 and PE are expressed by neutrophils, which provides a self-generating accumulation loop for the production of PGP and homing of neutrophils. Similar tot the human disease, expression of both proteases and PGP itself were elevated in the dextran sodium sulfate (DSS) mouse model of IBD. To examine if PGP could be used as a treatment target both a complementary peptide, L-arginine-threonine-arginine (RTR) which has been shown to bind to PGP sequences, and an anti-PGP antibody were injected into mice with colitis. Both treatments lead to reductions in severity of the DSS-colitis in these mice, confirming the importance of the collagen breakdown products in IBD, and opens new venues for the treatment of IBD in humans.