Neuropeptide Y (NPY) modulates Dextran Sodium Sulfate (DSS) ‐induced colitis

Neuropeptide Y (NPY) is an important neurotransmitter produced by the myenteric and sub mucosal neurons of the enteric nervous system. In this study we assessed the role of NPY in modulating the inflammation associated with DSS colitis. Colitis was induced by oral administration of 3% Dextran sodium sulphate (DSS) in NPY wild type (WT) mice and mice genetically deficient in NPY (NPY −/− ). Age and sex matched WT and NPY −/− mice receiving water served as controls. DSS increased NPY expression in the colon as examined by RT‐PCR and immunofluorescence. Severe inflammation was observed in NPY WT mice (Clinical score 8 ± 0.5) as compared to NPY −/− mice (2± 0.5) (P<0.01). H/E staining of colon revealed that WT mice had more crypt damage, inflammatory infiltrate and ulcerations (histological score−6.58 + 0.30) than NPY −/− mice (1.75 + 0.38). The neuronal nitric oxide synthase expression was up regulated in WT mice (P<0.05) but not in NPY −/− mice. Catalase activity, colonic GSH and nitrite were higher in WT mice indicating more oxidative stress. NPY, in vitro, also promoted more TNF‐α production (47%) from rat enteric neuronal cultures compared to untreated cultures (26%). The longitudinal muscle strips from DSS‐ treated WT mice exhibited impaired relaxation responses when compared to the controls (P<0.001). Thus, our findings highlight the role of NPY from enteric neurons as powerful modulators of inflammatory process in colitis.