| First Author | Tsung A | Year | 2007 |
| Journal | J Leukoc Biol | Volume | 81 |
| Issue | 1 | Pages | 119-28 |
| PubMed ID | 17062605 | Mgi Jnum | J:117230 |
| Mgi Id | MGI:3695841 | Doi | 10.1189/jlb.0706468 |
| Citation | Tsung A, et al. (2007) Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. J Leukoc Biol 81(1):119-28 |
| abstractText | Endogenous ligands released from damaged cells, so-called damage-associated molecular pattern molecules (DAMPs), activate innate signaling pathways including the TLRs. We have shown that hepatic, warm ischemia and reperfusion (I/R) injury, generating local, noninfectious DAMPs, promotes inflammation, which is largely TLR4-dependent. Here, we demonstrate that increasing dendritic cell (DC) numbers enhance inflammation and organ injury after hepatic I/R. High-mobility group box 1 (HMGB1), a NF released by necrotic cells or secreted by stimulated cells, is one of a number of ligands promoting TLR4 reactivity. Augmentation of DC numbers in the liver with GM-CSF hydrodynamic transfection significantly increased liver damage after I/R when compared with controls. TLR4 engagement on hepatic DC was required for the I/R-induced injury, as augmentation of DC numbers in TLR4 mutant (C3H/HeJ) mice did not worsen hepatic damage. It is interesting that TLR4 expression was increased in hepatic DC following HMGB1 stimulation in vitro, suggesting a mechanism for the increased liver injury following I/R. It thus appears that functional TLR4 on DC is required for I/R-induced injury. Furthermore, HMGB1 may direct the inflammatory responses mediated by DC, at least in part, by enhancing TLR4 expression and reactivity to it and other DAMPs. |
