Poly-γ-Glutamic Acid Attenuates Angiogenesis and Inflammation in Experimental Colitis

Poly-gamma-glutamic acid (gamma-PGA), naturally secreted from various strains of Bacillus, has anti-inflammatory activity. In inflammatory bowel disease (IBD), inflammation is promoted and sustained by angiogenesis; however, the role played by gamma-PGA in this condition is unclear. Therefore, we evaluated gamma-PGA effects on angiogenesis and inflammation in a dextran sulfate sodium-(DSS-) induced mouse colitis model. Experimental colitis was induced in male C57BL/6 mice by administering 3% DSS. Disease activity index (DAI), histopathological scores, microvascular density, myeloperoxidase activity, and VEGF-A and VEGFR2 expression were compared among control mice, DSS-treated mice, and mice receiving 3% DSS along with gamma-PGA at 50 mg/kg body weight per day or 3% DSS with gamma-PGA at 200 mg/kg bodyweight per day. We found that gamma-PGA significantly attenuated weight loss, DAI, and colon shortening. gamma-PGA also significantly reduced histopathological evidence of injury. Moreover, gamma-PGA significantly attenuated DSS-induced blood vessel densities. Furthermore, gamma-PGA attenuated DSS-induced expression of VEGF-A and its receptor, VEGFR2. In addition, gamma-PGA treatment led to reduced recruitment of leukocytes to the inflamed colon. Therefore, our results indicate that gamma-PGA has potential application in conditions marked by inflammatory-driven angiogenesis and mucosal inflammation.