Peptide YY 3–36 attenuates trinitrobenzene sulfonic acid-induced colitis in mice by modulating Th1/Th2 differentiation

Abstract

ABSTRACT Peptide YY (PYY) 3–36, the main circulatory form of PYY, plays important roles in gastrointestinal motility, secretion, and absorption. However, it is unknown whether PYY 3–36 has underlying functions in colitis. The Crohn’s disease (CD)-like mouse model in which CD is induced by trinitrobenzene sulfonic acid (TNBS) was established and utilized to investigate this potential role for PYY 3–36. The results showed that the expression of colonic mucosal PYY and PYY receptors Y1, Y2, Y4 were significantly increased in mice with TNBS-induced colitis. In vitro, PYY 3–36 remarkably inhibited the production of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from lipopolysaccharide (LPS)-induced macrophages. In vivo, a high concentration of PYY 3–36 robustly decreased the weight loss and death rate and attenuated the pathological colon tissue damage observed in mice with TNBS-induced colitis. Further studies uncovered that PYY 3–36 treatment reduced the levels of colon myeloperoxidase (MPO) and both colonic and systemic TNF-α and IL-6 observed in murine colitis. Furthermore, flow cytometric analysis showed PYY 3–36 altered the proportion of Th1/Th2 splenocytes in the disease model of colitis. Collectively, these results suggest that PYY 3–36 may be a promising candidate for the improvement of colitis, reflected by the attenuation of colon inflammatory responses observed in experimental murine colitis.