Interleukin-1β induces the expression of aquaporin-4 through a nuclear factor-κB pathway in rat astrocytes

Interleukin (IL)-1 beta is known to play a role in the formation of brain edema after various types of injury. Aquaporin (AQP)4 is also reported to be involved in the progression of brain edema. We tested the hypothesis that AQP4 is induced in response to IL-1 beta. We found that expression of AQP4 mRNA and protein was significantly up-regulated by IL-1 beta in cultured rat astrocytes, and that intracerebroventricular administration of IL-1 beta increased the expression of AQP4 protein in rat brain. The effects of IL-1 beta on induction of AQP4 were concentration and time dependent. The effects of IL-1 beta on AQP4 were mediated through IL-1 beta receptors because they were abolished by co-incubation with IL-1 receptor antagonist. It appeared that IL-1 beta increased the level of AQP4 mRNA without involvement of de novo protein synthesis because cycloheximide, a protein synthesis inhibitor, did not inhibit the effects of IL-1 beta. Inhibition of the nuclear factor-kappa B (NF-kappa B) pathway blocked the induction of AQP4 by IL-1 beta in a concentration-dependent manner. These findings show that IL-1 beta induces expression of AQP4 through a NF-kappa B pathway without involvement of de novo protein synthesis in rat astrocytes.