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

Interleukin-6 (IL-6) is increased in brain of aged mice. The purpose of thi s study was to determine if binding of nuclear factor kappaB (NF kappaB) 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 juve nile mice. Competitive RT-PCR showed that IL-6 mRNA concentration was at le ast 4-fold higher in aged brain compared to adult brain. Next, binding of t he transcription factor NF kappaB to the IL-6 promoter in brains of 1-, 6-, and 24-month-old mice was determined. Electrophoretic mobility shift assay showed that NF kappaB activity was increased in aged brain compared to adu lt and juvenile brain. Moreover, glial cells cultured from aged mice showed more NF kappaB DNA-binding activity and more IL-6 mRNA and protein express ion than glia from adults. However, incubating glia from aged mice in the p resence Of kappaB decoy inhibited these effects of age. The same was observ ed in vivo as intracerebroventricular injection Of kappaB decoy in aged mic e decreased NF kappaB activity and IL-6 mRNA and protein in brain. These re sults show that the DNA-binding activity of NF kappaB is increased in the b rain of aged mice and that at least one consequence is increased expression of IL-6. (C) 2001 Elsevier Science B.V. All rights reserved.