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Open Access Highly Accessed Research article

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

Christelle Monville1, Christiane Fages1, Anne-Marie Feyens2, Véronique d'Hondt2, Catherine Guillet3, Ann Vernallis4, Hugues Gascan3 and Marc Peschanski1*

Author Affiliations

1 INSERM U421/IM3, Créteil, France

2 Université Catholique de Louvain, Bruxelles, Belgium

3 INSERM E9928, CHU Angers, France

4 Aston University, Birmingham, United Kingdom

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BMC Cell Biology 2002, 3:20  doi:10.1186/1471-2121-3-20

Published: 31 July 2002

Abstract

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.

Keywords:
differentiation; IL-6-type cytokines; astrogliosis; multi-drug resistance