Mo2024 Recombinant Thrombomodulin Modulates Murine Colitis via Inhibition of HMGB1

and activity of myeloperoxidase. Results: While healthy controls gained weight during the experiment (+8.1%±1.9), untreated colitis animals significantly lost weight (-6.8%±3.0). Animals treated with MSA or gp96 showed a diminished relative loss of body weight (2.4%±2.3, and -0.4%±2.0, respectively). Endoscopic analysis of inflammation (MEICS score) revealed strong sings of inflammation in untreated colitis animals (3.8±0.8) compared to healthy controls (0.3±0.3). Also MSA treated animals showed strong changes (2.8±0.1), while gp96 treatment restored macroscopic signs of inflammation (1.5±0.8). Strong histological signs of inflammation were seen in untreated animals suffering from colitis (3.4±0.2), compared to healthy controls (0.0±0.0). Treatment with gp96 resulted in ameliorated histological signs of inflammation (2.2±0.3). Relative spleen weight of untreated colitis animals was found to be significantly increased (8.1±4.0) compared to healthy controls (1.5±0.8). While treatment with MSA even increased the effect (7.3±1.3), gp96 treatment restored relative spleen weight (2.6±0.8). Gene expression profiles of colonic specimen revealed lower levels of TNFα (0.7-fold) and IFN γ (0.5-fold) in gp96 treated animals than in untreated colitis animals. Myeloperoxidase activity was used as a quantitative assessment of neutrophil infiltration. While healthy controls showed the lowest activity (0.05±0.00), it was increased in untreated (0.13±0.04) and MSA treated (0.09±0.02) colitis animals. gp96 treated animals (0.04±0.01) showed activity comparable to healthy controls. Conclusion: Our observations show that gp96 treatment ameliorates experimental transfer colitis. gp96 might affect naive T cells epigenetically, exerting a memory effect. A deeper understanding of the underlying regulatorymechanisms will essentially contribute to reveal new therapeutic treatment options.