Interleukin-1beta induces the expression of aquaporin-4 through a nuclear factor-kappaB pathway in rat astrocytes.
Interleukin (IL)-1beta 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-1beta. We found that expression of AQP4 mRNA and protein was significantly up-regulated by IL-1beta in cultured rat astrocytes, and that intracerebroventricular administration of IL-1beta increased the expression of AQP4 protein in rat brain. The effects of IL-1beta on induction of AQP4 were concentration and time dependent. The effects of IL-1beta on AQP4 were mediated through IL-1beta receptors because they were abolished by co-incubation with IL-1 receptor antagonist. It appeared that IL-1beta 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-1beta. Inhibition of the nuclear factor-kappaB (NF-kappaB) pathway blocked the induction of AQP4 by IL-1beta in a concentration-dependent manner. These findings show that IL-1beta induces expression of AQP4 through a NF-kappaB pathway without involvement of de novo protein synthesis in rat astrocytes.
Ito
Hiroaki
H
Department of Anesthesiology and Medical Crisis Management, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
Yamamoto
Naoki
N
Arima
Hajime
H
Hirate
Hiroyuki
H
Morishima
Tetsuro
T
Umenishi
Fuminori
F
Tada
Toyohiro
T
Asai
Kiyofumi
K
Katsuya
Hirotada
H
Sobue
Kazuya
K
D020121:5' Untranslated Regions; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D017931:DNA Primers; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020121:5' Untranslated Regions; C496030:AQP4 protein, human; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D017931:DNA Primers; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger