Involvement of high mobility group box 1 in the pathogenesis of severe hemolytic uremic syndrome in a murine model.

Typical hemolytic uremic syndrome is caused by Shiga toxin (Stx2) and lipopolysaccharide (LPS) of and leads to acute kidney injury. The role of innate immunity in this pathogenesis is unclear. We analyzed the role of high mobility group box 1 (HMGB1) at the onset of disease in a murine model. C57BL/6 mice were intraperitoneally administered saline (), anti-HMGB1 monoclonal antibody (), Stx2 and LPS to elicit severe disease (), or Stx2, LPS, and anti-HMGB1 antibody (). While all mice in died by of the experiment, all mice in survived. Anemia and thrombocytopenia were pronounced and plasma creatinine levels were significantly elevated in only at 72 h. While at 72 h after toxin administration the glomerulus tissue in showed pathology similar to that of humans, mesangial cell proliferation was seen in . Plasma HMGB1 levels in peaked 3 h after administration and were higher than those in other groups. Expression of the receptor of advanced glycation end products and NF-κB, involved in HMGB1 signaling, was significantly elevated in but not in . Administration of anti-HMGB1 antibody in a murine model of severe disease inhibited plasma HMGB1 and promoted amelioration of tissue damage. HMGB1 was found to be involved in the disease pathology; therefore, controlling HMGB1 activity might inhibit disease progression.