NR AQWM
AU Schultz,J.; Schwarz,A.; Neidhold,S.; Burwinkel,M.; Riemer,C.; Simon,D.; Kopf,M.; Otto,M.; Baier,M.
TI Role of interleukin-1 in prion disease-associated astrocyte activation
QU American Journal of Pathology 2004 Aug; 165(2): 671-8
PT journal article
AB Prion-induced chronic neurodegeneration has a substantial inflammatory component, and the activation of glia cells may play an important role in disease development and progression. However, the functional contribution of cytokines to the development of the gliosis in vivo was never systematically studied. We report here that the expression of interleukin-1ß (IL-1ß), IL-1ß-converting enzyme, and IL-1 receptor type 1 (IL-1RI) is up-regulated in a murine scrapie model. The scrapie-induced gliosis in IL-1RI(-/-) mice was characterized by an attenuated activation of astrocytes in the asymptomatic stage of the disease and a reduced expression of CXCR3 ligands. Furthermore, the accumulation of the misfolded isoform of the prion protein PrPsc was significantly delayed in the IL-1RI(-/-) mice. These observations indicate that IL-1 is a driver of the scrapie-associated astrocytosis and possibly the accompanying amyloid deposition. In addition, scrapie-infected IL-1RI-deficient (IL-1RI(-/-)) mice showed a delayed disease onset and significantly prolonged survival times suggesting that an anti-inflammatory therapeutical approach to suppress astrocyte activation and/or glial IL-1 expression may help to delay disease onset in established prion infections of the central nervous system.
IN Schultz et al. fanden in Scrapie-infizierten Mäusen eine verstärkte Expression von Interleukin-1ß (IL-1ß), dem IL-1ß konvertierenden Enzyme und des IL-1-Rezeptors Type 1 (IL-1RI). In Scrapie-infizierten Hausmäusen ohne IL-1RI-Expression waren die präklinische Astrozyten-Aktivierung abgeschwächt, die PrPsc-Akkumulation verzögert und die Inkubationszeit sowie die Krankheitsphasen verlängert.
MH Animals; Astrocytes/*metabolism/pathology; Caspase 1/*metabolism; Comparative Study; Disease Models, Animal; Gliosis/*etiology; Interleukin-1/*metabolism; Ligands; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia/pathology; PrPsc Proteins/metabolism; Prion Diseases/*metabolism/pathology; Receptors, Chemokine/metabolism; Receptors, Interleukin-1/genetics/*physiology; Support, Non-U.S. Gov't; Survival Rate; Up-Regulation
AD Project "Neurodegenerative Diseases," Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
SP englisch
PO USA