Regulation of interleukin-6 gene expression in brain of aged mice by nuclear factor κB

Abstract

Interleukin-6 (IL-6) is increased in brain of aged mice. The purpose of this study was to determine if binding of nuclear factor κB (NFκB) to the IL-6 promoter is responsible for the age-related increase in brain IL-6. In an initial study, the effect of age on IL-6 in brain was verified as IL-6 protein was increased in brain of aged mice compared to adult and juvenile mice. Competitive RT-PCR showed that IL-6 mRNA concentration was at least 4-fold higher in aged brain compared to adult brain. Next, binding of the transcription factor NFκB to the IL-6 promoter in brains of 1-, 6-, and 24-month-old mice was determined. Electrophoretic mobility shift assay showed that NFκB activity was increased in aged brain compared to adult and juvenile brain. Moreover, glial cells cultured from aged mice showed more NFκB DNA-binding activity and more IL-6 mRNA and protein expression than glia from adults. However, incubating glia from aged mice in the presence of κB decoy inhibited these effects of age. The same was observed in vivo as intracerebroventricular injection of κB decoy in aged mice decreased NFκB activity and IL-6 mRNA and protein in brain. These results show that the DNA-binding activity of NFκB is increased in the brain of aged mice and that at least one consequence is increased expression of IL-6.