| First Author | Austermann J | Year | 2014 |
| Journal | Cell Rep | Volume | 9 |
| Issue | 6 | Pages | 2112-23 |
| PubMed ID | 25497086 | Mgi Jnum | J:222660 |
| Mgi Id | MGI:5645186 | Doi | 10.1016/j.celrep.2014.11.020 |
| Citation | Austermann J, et al. (2014) Alarmins MRP8 and MRP14 induce stress tolerance in phagocytes under sterile inflammatory conditions. Cell Rep 9(6):2112-23 |
| abstractText | Hyporesponsiveness by phagocytes is a well-known phenomenon in sepsis that is frequently induced by low-dose endotoxin stimulation of Toll-like receptor 4 (TLR4) but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins MRP8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner that results in enhanced survival to septic shock in mice. During sterile inflammation, polytrauma and burn trauma patients initially present with high serum concentrations of myeloid-related proteins (MRPs). Human neonatal phagocytes are primed for hyporesponsiveness by increased peripartal MRP concentrations, which was confirmed in murine neonatal endotoxinemia in wild-type and MRP14(-/-) mice. Our data therefore indicate that alarmin-triggered phagocyte tolerance represents a regulatory mechanism for the susceptibility of neonates during systemic infections and sterile inflammation. |
