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

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

author email corresponding author email

BMC Cell Biology 2002, 3:20doi: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.