Increased expression of mRNA encoding interleukin-1? and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration

Authors:
Publisher website
Google Scholar
Abstract
Kainic acid, an analogue of glutamate, injected systemically to rats evokes seizures that are accompanied by nerve cell damage primarily in the limbic system. In the present study, we have analyzed the temporal profile of the expression of the cytokines interleukin‐1β (IL‐1β) and IL‐1 receptor antagonist (IL‐1ra), and the related IL‐1β‐converting enzyme (ICE/caspase‐1), in different regions of the rat brain in response to peripheral kainic acid administration (10 mg/kg, i.p.). In situ hybridization histochemistry experiments revealed that IL‐1β mRNA–expressing cells, morphologically identified as microglial cells, were mainly localized to regions showing pronounced neuronal degeneration; hippocampus, thalamus, amygdala, and certain cortical regions. The strongest expression of IL‐1β mRNA was observed after 12 hr in these regions. A weak induction of the IL‐1β mRNA expression was observed already at 2 hr. Similar results were obtained by RT‐PCR analysis, showing a significantly increased expression of IL‐1β mRNA in the hippocampus and amygdala after 12 hr. In addition, RT‐PCR analysis revealed that IL‐1ra mRNA, and specifically mRNA encoding the secreted isoform of IL‐1ra (sIL‐1ra), was strongly induced in the hippocampus and amygdala at 12 and 24 hr post‐injection. RT‐PCR analysis of mRNA encoding caspase‐1 showed a significantly increased expression in the amygdala after 12 hr. In conclusion, in response to systemic kainic acid injection IL‐1β mRNA is rapidly induced and followed by induction of IL‐1ra mRNA and caspase‐1 mRNA, supporting a role of the IL‐1 system in the inflammatory response during excitotoxic damage. J. Neurosci. Res. 60:266–279, 2000

This publication has 89 references indexed in Scilit: