Astroglial expression of the P-glycoprotein is controlled by intracellular CNTF


Background - The P-glycoprotein (P-gp), an ATP binding cassette transmembrane transporter, is expressed by astrocytes in the adult brain, and is positively modulated during astrogliosis. In a search for factors involved in this modulation, P-gp overexpression was studied in long-term in vitro astroglial cultures. Results - Surprisingly, most factors that are known to induce astroglial activation in astroglial cultures failed to increase P-gp expression. The only effective proteins were IFNγ and those belonging to the IL-6 family of cytokines (IL-6, LIF, CT-1 and CNTF). As well as P-gp expression, the IL-6 type cytokines - but not IFNγ - stimulated the expression of endogenous CNTF in astrocytes. In order to see whether an increased intracellular level of CNTF was necessary for induction of P-gp overexpression by IL-6 type cytokines, by the same cytokines analysis was carried out on astrocytes obtained from CNTF knockout mice. In these conditions, IFNγ produced increased P-gp expression, but no overexpression of P-gp was observed with either IL-6, LIF or CT-1, pointing to a role of CNTF in the intracellular signalling pathway leading to P-gp overexpression. In agreement with this suggestion, application of exogenous CNTF -which is internalised with its receptor - produced an overexpression of P-gp in CNTF-deficient astrocytes. Conclusions - These results reveal two different pathways regulating P-gp expression and activity in reactive astrocytes, one of which depends upon the intracellular concentration of CNTF. This regulation of P-gp may be one of the long searched for physiological roles of CNTF.

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Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
Additional Information: © 2002 Monville et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Uncontrolled Keywords: differentiation,IL-6-type cytokines,astrogliosis,multi-drug resistance ,Cytokines
Publication ISSN: 1471-2121
Last Modified: 05 Apr 2024 07:08
Date Deposited: 08 Dec 2014 11:10
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Related URLs: http://www.biom ... /1471-2121/3/20 (Publisher URL)
PURE Output Type: Article
Published Date: 2002-07-31
Authors: Monville, Christelle
Fages, Christiane
Feyens, Anne-Marie
D'Hondt, Véronique
Guillet, Catherine
Vernallis, Ann
Gascan, Hugues
Peschanski, Marc



Version: Published Version

License: Creative Commons Attribution

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