RT Journal Article
SR Electronic
T1 Induction of IκBα mRNA Expression in the Brain by Glucocorticoids: A Negative Feedback Mechanism for Immune-to-Brain Signaling
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6473
OP 6477
DO 10.1523/JNEUROSCI.20-17-06473.2000
VO 20
IS 17
A1 Ning Quan
A1 Lingli He
A1 Wenmin Lai
A1 Tiansheng Shen
A1 Miles Herkenham
YR 2000
UL http://www.jneurosci.org/content/20/17/6473.abstract
AB Peripheral injection of bacterial endotoxin lipopolysaccharide (LPS) induces brain mRNA expression of the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α and the cytokine-responsive immediate-early gene IκBα. Peripheral LPS also increases levels of plasma glucocorticoids. Whether the induction of IκBα mRNA in the brain after peripheral LPS injection is caused by the feedback action of glucocorticoids has not been determined. In this study, we examined the mRNA expression of IκBα and IL-1β in the rat brain by in situ hybridization histochemistry. Injection of the glucocorticoid agonist dexamethasone induced IκBα mRNA expression in the brain in a pattern identical to that of LPS injection. LPS but not dexamethasone also induced IL-1β mRNA expression. Pretreatment with dexamethasone 30 min before LPS injection enhanced the expression of IκBα mRNA in the brain in a dose-dependent manner. Immobilization of rats for 2 hr (which raises glucocorticoid levels) also induced IκBα mRNA expression without inducing the expression of IL-1β. Brain IκBα expression induced by peripheral LPS injection was attenuated by pretreatment of rats with the glucocorticoid antagonist RU-486. Finally, increased expression of IL-1β mRNA in the brain was observed at 4 hr after peripheral LPS injection in adrenalectomized rats compared with sham-operated rats. These results reveal that in the brain glucocorticoids selectively induce IκBα mRNA expression, which serves as a negative feedback mechanism for peripheral LPS-induced synthesis of proinflammatory cytokines. Such an inhibitory control mechanism may be important for preventing prolonged expression of proinflammatory cytokines in the brain after peripheral immune challenge.