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Effect of 5637-conditioned medium and recombinant cytokines on P-glycoprotein expression in a human GM-CSF-dependent leukemic myeloid cell line.

Abstract : This study was aimed at evaluating the influence of 5637-conditioned medium (5637-CM) and human recombinant cytokines on both expression and function of P-glycoprotein (P-gp) in TF-1, a GM-CSF/IL-3-dependent acute myeloid leukemia cell line which constitutively expresses functional P-gp. P-gp expression was measured by flow cytometry using MRK16 monoclonal antibody. P-gp function was measured by rhodamine 123 (Rh 123) efflux kinetics. When TF-1 cells were cultured with 5637-CM (50% v/v), both P-gp expression and P-gp efflux capacity were increased in a time-dependent manner with a 4-fold increase in P-gp expression level at day 6 whereas TF-1 cell differentiation status remained unchanged as assessed by morphological studies, phenotypical and cytochemistry analysis. Recombinant cytokines including GM-CSF, G-CSF, IL-1 beta, IL-6, stem cell factor, LIF, erythropoietin, and IL-3 had no effect on P-gp expression whereas TNF alpha induced dose- and time-dependent P-gp and mdr-1 gene overexpression. However, TNF alpha-induced P-gp overexpression had no influence on P-gp efflux capacity. Furthermore, when TF-1 cells were exposed to IL-3 for periods longer than 1 month, we found that P-gp efflux capacity was increased as compared to cells cultured with GM-CSF whereas P-gp expression was unchanged. Both TNF alpha and IL-3 did not induce TF-1 differentiation. Collectively, these results suggest that cytokines may influence both expression and function of P-gp in TF-1 cells without interfering with their differentiation status. In contrast to cytokines, phorbol esters enhanced expression and efflux capacity of P-gp in parallel with TF-1 cell monocytic differentiation. Finally, our study suggests that paracrine and/or autocrine secretion of cytokines may interfere with P-gp activity in some acute myeloid leukemia cells.
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Journal articles
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https://www.hal.inserm.fr/inserm-02438206
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:24:45 AM
Last modification on : Wednesday, July 15, 2020 - 10:26:01 AM

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  • HAL Id : inserm-02438206, version 1
  • PUBMED : 7564516

Citation

J Bailly, P. Pourquier, J Jaffrézou, E Duchayne, G Cassar, et al.. Effect of 5637-conditioned medium and recombinant cytokines on P-glycoprotein expression in a human GM-CSF-dependent leukemic myeloid cell line.. Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 1995, 9 (10), pp.1718-25. ⟨inserm-02438206⟩

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