| First Author | Wu H | Year | 2010 |
| Journal | J Am Soc Nephrol | Volume | 21 |
| Issue | 11 | Pages | 1878-90 |
| PubMed ID | 20847143 | Mgi Jnum | J:185901 |
| Mgi Id | MGI:5430476 | Doi | 10.1681/ASN.2009101048 |
| Citation | Wu H, et al. (2010) HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol 21(11):1878-90 |
| abstractText | High-mobility group box 1 (HMGB1), a nuclear factor released extracellularly as an inflammatory cytokine, is an endogenous ligand for Toll-like receptor 4 (TLR4). TLR4 activation mediates kidney ischemia-reperfusion injury (IRI), but whether HMGB1 contributes to IRI is unknown. Here, treating wild-type mice with neutralizing anti-HMGB1 antibody protected them against kidney IRI, evidenced by lower serum creatinine and less tubular damage than untreated mice. Mice treated with anti-HMGB1 had significantly less tubulointerstitial infiltration by neutrophils (day 1) and macrophages (day 5) and markedly reduced apoptosis of tubular epithelial cells. Furthermore, anti-HMGB1 antibody-treated IRI kidneys had significantly lower levels of IL-6, TNFalpha, and monocyte chemoattractant protein 1 (MCP1). mRNA, which are downstream of HMGB1. Conversely, administration of rHMGB1 after reperfusion exacerbated kidney IRI in wild-type mice. TLR4 deficient (TLR4(-/-)) mice were protected against kidney IRI; administration of neither anti-HMGB1 antibody nor rHMGB1 affected this renoprotection. In conclusion, endogenous HMGB1 promotes kidney damage after IRI, possibly through the TLR4 pathway. Administration of a neutralizing antibody to HMGB1 either before or soon after ischemia-reperfusion affords significant protection, suggesting therapeutic potential for acute kidney injury. |
