Roles of high-mobility group box 1 in murine experimental colitis.

High-mobility group box 1 (HMGB1) plays a role in inflammatory and immune-mediated diseases. This study investigated the role of HMGB1 in colonic inflammation. Colitis was induced by orally feeding mice 4.5% dextran sulfate sodium (DSS) for up to 7 days. Mice were sacrificed on days 0, 3, 7 and 10, and the colon harvested for the measurement of HMGB1 and pro-inflammatory cytokines. To block HMGB1 induction, an anti-HMGB1 antibody was administered intraperitoneally 2 h before or 3 days after the induction of colitis, and disease severity was assessed by clinical and histological scoring. The colonic levels of tumor necrosis factor-α and interleukin-1β were elevated in relation to disease severity. The level of HMGB1 increased more slowly than that of the cytokines. Immunohistochemical study of the colons showed that the tissues of mice treated with DSS had a higher expression of HMGB1 and its receptor - the receptor for advanced glycation end products - than normal controls, especially in inflammatory infiltrates. The anti-HMGB1 antibody ameliorated tissue damage. In conclusion, HMGB1 is an important mediator of colonic inflammation, and suppression of this protein partially protects against colonic inflammation.