Removal of HMGB1 in inflammatory bowel disease using DNA-beads. (P5197)

Abstract

Inflammatory bowel disease (IBD) affects millions of Americans, and costs 1.7 billion annually. High mobility group box 1 (HMGB1) is a cytokine mediator of inflammation in the pathogenesis of IBD. Elevated levels of HMGB1 have been observed in human IBD and in mouse models of colitis (Vitali R, et al. Am J Gastroenterol. 2011. Yamasaki H, et al. Mol Med Report. 2009). Blocking HMGB1 induction by either anti-HMGB1 antibody or ethyl pyruvate (HMGB1 inhibitor) was able to ameliorate the inflammation in colitis mice. DNA with certain sequences or structures has been shown with high affinity binding to HMGB1, and has been reported to attenuate inflammatory responses by blocking HMGB1. In this study, we conjugated DNA sequences to sepharose beads and utilized them as novel reagents to remove HMGB1. We found that the DNA-beads were able to bind HMGB1 with a capacity of 7.6 μmol/L, and each immobilized DNA molecule was able to bind three HMGB1 molecules (DNA:HMGB1 ratio = 1:3). DNA-beads were able to capture HMGB1 from RAW 264.7 cell supernatant stimulated with LPS and from sera of septic mice induced by cecal ligation and puncture. When applied to stools of mice with dextran sulfate sodium (DSS) induced colitis, DNA-beads were able to capture HMGB1 from stools of these colitis mice. Hence, our data suggest a therapeutic potential for DNA-beads to remove HMGB1 in inflammatory diseases such as IBD.