The protective and anti-inflammatory effects of a modified glucagon-like peptide-2 dimer in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting inflammatory disease resulting from immune dysregulation in the gut. As a clinically frequent disease, it can affect individuals throughout their lives, with multiple complications. Glucagon-like peptide 2 (GLP-2) is a potent epithelium-specific intestinal growth factor. However, native GLP-2 has a relatively short half-life in human circulation because of extensive renal clearance and rapid degradation by the proteolytic enzyme dipeptidyl peptidase-IV (DPP-IV). Previously, We prepared a recombinant GLP-2 variant (GLP-22), which has increased half-life and activity as compared to the [Gly(2)]GLP-2 monomer. The aim of the present study was to investigate the protective potential of GLP-22 in IBD models. LPS-induced in vitro model and dextran sulfate sodium (DSS)-induced in vivo model were used to study the anti-inflammatory and therapeutic effect of GLP-22. We found that treated with GLP-2 showed a significantly reduction in the secretion of inflammatory cytokines. Furthermore, GLP-22 alleviated symptoms of DSS-induced colitis. GLP-22 treated mice displayed an increase in body weight, lower colitis scores, and fewer mucosal damage compared with GLP-2 treated mice. MPO activities, protein expression of NLRP3 and COX2 in the colon tissues were significantly reduced in GLP-22 groups. Importantly, the ameliorative effect of GLP-22 was related to anti-apoptosis effect in colon tissues. These findings demonstrated that GLP-22 may offer a superior therapeutic benefit over [Gly(2)]GLP-2 monomer for treatment of IBD.