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

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 IFNgamma 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 IFNgamma) 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, IFNgamma 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. CONCLUSION: 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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https://www.hal.inserm.fr/inserm-00123527
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Submitted on : Thursday, January 11, 2007 - 11:04:25 AM
Last modification on : Thursday, March 5, 2020 - 10:10:07 AM
Long-term archiving on: : Friday, September 21, 2012 - 10:01:13 AM

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  • HAL Id : inserm-00123527, version 1
  • PUBMED : 12150717

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Christelle Monville, Christiane Fages, Anne-Marie Feyens, Veronique d'Hondt, Catherine Guillet, et al.. Astroglial expression of the P-glycoprotein is controlled by intracellular CNTF.. BMC Cell Biology, BioMed Central, 2002, 3, pp.20. ⟨inserm-00123527⟩

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