Astrocytic ceruloplasmin expression, which is induced by IL-1beta and by traumatic brain injury, increases in the absence of the IL-1 type 1 receptor.

Autor: Kuhlow CJ; Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA., Krady JK, Basu A, Levison SW
Jazyk: angličtina
Zdroj: Glia [Glia] 2003 Oct; Vol. 44 (1), pp. 76-84.
DOI: 10.1002/glia.10273
Abstrakt: IL-1alpha and IL-1beta are induced immediately after insults to the brain, and signaling through the type 1 IL-1 receptor is essential for a normal microglial and astroglial response to injury. To better understand which genes are induced in astrocytes by IL-1beta, we used the unbiased technique of differential display to analyze mouse astroglial gene expression after IL-1beta treatment. Two novel genes were induced, as well as the gene for ceruloplasmin, a ferroxidase with antioxidant properties. Ceruloplasmin was analyzed further by Northern and Western blot. RNA and protein levels of ceruloplasmin were increased when astrocytes were treated with IL-1beta. To determine whether the IL-1 type 1 receptor (IL-1R1) is essential for the injury-induced expression of ceruloplasmin, a Western blot analysis was performed after a traumatic brain injury on mice that were IL-1R1-deficient. Ceruloplasmin increased significantly above controls after injury; however, injury-induced levels of ceruloplasmin were lower in IL-1R1-deficient (2.7-fold increase) than in the wild-type animals (3.5-fold increase). These data indicate that while IL-1R1 deletion has a slight effect on ceruloplasmin expression, it is not essential for either the basal or the induced expression of ceruloplasmin in vivo. Since ceruloplasmin buffers free copper, oxidizes ferrous iron, and catalyzes the dismutation of free radicals, increased levels of ceruloplasmin likely protect neurons and glia from sustaining damage after injury. Furthermore, as the IL-1R1 has been proposed to be a target for achieving neuroprotection after injury, these data suggest that the protection afforded by ceruloplasmin will be retained even when the IL-1R1 is antagonized.
(Copyright 2003 Wiley-Liss, Inc.)
Databáze: MEDLINE
Externí odkaz: