| First Author | Xu J | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 5 | Pages | 2626-31 |
| PubMed ID | 21784973 | Mgi Jnum | J:179148 |
| Mgi Id | MGI:5301205 | Doi | 10.4049/jimmunol.1003930 |
| Citation | Xu J, et al. (2011) Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol 187(5):2626-31 |
| abstractText | We previously reported that extracellular histones are major mediators of death in sepsis. Infusion of extracellular histones leads to increased cytokine levels. Histones activate TLR2 and TLR4 in a process that is enhanced by binding to DNA. Activation of TLR4 is responsible for the histone-dependent increase in cytokine levels. To study the impact of histone release on pathology we used two models: a Con A-triggered activation of T cells to mimic sterile inflammation, and acetaminophen to model drug-induced tissue toxicity. Histones were released in both models and anti-histone Abs were protective. TLR2- or TLR4-null mice were also protected. These studies imply that histone release contributes to death in inflammatory injury and in chemical-induced cellular injury, both of which are mediated in part through the TLRs. |
