Document Detail


Diclofenac Enhances Proinflammatory Cytokine-Induced Aquaporin-4 Expression in Cultured Astrocyte.
MedLine Citation:
PMID:  23322320     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Acute encephalopathy is a generic term for acute brain dysfunction occurring after infection. Acute encephalopathy induced by influenza virus results in high mortality, and most cases of influenza-associated encephalopathy (IAE) result in brain edema. Administration of diclofenac sodium (DCF), a non-steroidal anti-inflammatory drug (NSAID), is associated with a significant increased mortality rate of IAE. These previous clinical findings proposed further investigation of DCF administration and brain edema to clarify how DCF aggravates IAE. Aquaporin-4 (AQP4) is the predominant water channel protein in the mammalian brain, and is mainly expressed in astrocytes. AQP4 plays an important role in brain water homeostasis. Therefore, we investigated a possible association between DCF and AQP4 production in astrocytes. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor α, and interferon γ, and then treated with DCF. DCF enhanced proinflammatory cytokine-induced AQP4 gene and protein expression in astrocytes, whereas DCF alone did not change the AQP4 gene expression. The addition of nuclear factor-kappa B (NF-κB) inhibitor abrogated AQP4 gene and protein expression completely in astrocytes treated with cytokines alone and in those also treated with DCF. In conclusion, this study demonstrated that AQP4 is upregulated in astrocyte by proinflammatory cytokines, and that the addition of DCF further augments AQP4 production. This effect is mediated via NF-κB signaling. The enhancement of AQP4 production by DCF may explain the significantly increased mortality rates in IAE patients treated with DCF.
Authors:
Hayato Asai; Hiroki Kakita; Mineyoshi Aoyama; Yoshiaki Nagaya; Shinji Saitoh; Kiyofumi Asai
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Cellular and molecular neurobiology     Volume:  -     ISSN:  1573-6830     ISO Abbreviation:  Cell. Mol. Neurobiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200709     Medline TA:  Cell Mol Neurobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Sexual Dimorphism in Expression of Insulin and Insulin-Like Growth Factor-I Receptors in Developing ...
Next Document:  Neuroprotective Effects of Estradiol on Motoneurons in a Model of Rat Spinal Cord Embryonic Explants...