Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer

S Maeda, Y Hikiba, W Shibata, T Ohmae… - Biochemical and …, 2007 - Elsevier
S Maeda, Y Hikiba, W Shibata, T Ohmae, A Yanai, K Ogura, S Yamada, M Omata
Biochemical and biophysical research communications, 2007Elsevier
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-κB activation. Two putative sources of HMGB1 were …
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-κB 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-κB 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.
Elsevier