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

Abstract

Interleukin (IL)-1b 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-1b. We found that expression of AQP4 mRNA and protein was significantly up-regulated by IL-1b in cultured rat astrocytes, and that intracerebroventricular administration of IL-1b increased the expression of AQP4 protein in rat brain. The effects of IL-1b on induction of AQP4 were concentration and time dependent. The effects of IL-1b on AQP4 were mediated through IL-1b receptors because they were abolished by co-incubation with IL-1 receptor antagonist. It appeared that IL-1b 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-1b. Inhibition of the nuclear factor-jB (NF-jB) pathway blocked the induction of AQP4 by IL-1b in a concentration-dependent manner. These findings show that IL-1b induces expression of AQP4 through a NF-jB pathway without involvement of de novo protein synthesis in rat astrocytes.

MicroRNA-130a Represses Transcriptional Activity of Aquaporin 4 M1 Promoter

“…S5). Contrary to the findings of Ito et al (29), Tourdias et al (30) showed opposing IL1␤ and AQP4 profiles in animal models. They reported that in inflammatory animal models IL1␤ expression in the brain peaked at day 1 and dropped back to basal levels by day 7.…”

“…(29) showed that increasing the interleukin-1␤ (IL1␤) concentration could mediate transcriptional activation of the AQP4 M1 promoter via the transcription factor nuclear factor B (NFB). However, no NFB binding site was identified on the AQP4 M1 promoter, suggesting an indirect effect by the transcription factor (29). We observed that removal of IL1␤ from cultured cells did not significantly affect AQP4 M1 expression.…”

Systemic Administration of Lipopolysaccharide Increases the Expression of Aquaporin-4 in the Rat Anterior Pituitary Gland

“…Second, LPS may act indirectly; these indirect effects may be mediated by LPS-induced pro-inflammatory cytokines, such as interleukin (IL)-1β. A previous study has demonstrated that IL-1β induces the expression of AQP4 through IL-1 receptor in rat primary astrocytes [7]. In the anterior pituitary gland, robust IL-1β mRNA induction has been demonstrated at 0.5 hr after peripheral LPS injection [16,19].…”

Role of aquaporins in cell proliferation: What else beyond water permeability?

“…Moreover, this transcription factor seems to regulate the expression of some AQPs and, in turn, control cell proliferation. [104][105][106][107] In addition, hypoxia-inducible trans-cription factors, HIF-1a or 2a, may take part in the proliferation mediated by AQPs. We have shown that stable overexpression of AQP1, 3 and 5 increases the stability of HIF-2a during chronic exposure to hypoxia 108,109 thereby increasing the expression of many genes implicated in activities relevant for tumor growth, such as glucose uptake and metabolism, angiogenesis, cell proliferation and apoptosis.…”