| First Author | Maeda S | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 360 |
| Issue | 2 | Pages | 394-400 |
| PubMed ID | 17599806 | Mgi Jnum | J:123028 |
| Mgi Id | MGI:3716258 | Doi | 10.1016/j.bbrc.2007.06.065 |
| Citation | Maeda S, et al. (2007) Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer. Biochem Biophys Res Commun 360(2):394-400 |
| abstractText | High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-kappaB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-kappaB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer. |
