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5-Lipoxygenase inhibitors potentiate 1α,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway

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Abstract

The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1α,25-dihydroxyvitamin D3 (VD3) induces differentiation toward the monocytic/macrophage lineage, demonstrated by the increased expression of CD11b and CD14, and the production of opsonized zymosan particles (OZP)-stimulated reactive oxygen species (ROS). Moreover, in more sensitive HL-60 cells, increased expression of 5-lipoxygenase (5-LPO), Mcl-1, IκB, and c-Jun, accompanied by the activation of p38 MAPK, was detected. These VD3 effects on HL-60 cell differentiation were significantly potentiated by 5-LPO inhibitors MK-886 and AA-861 and were inverted by SB202190 (SB), a p38 MAPK inhibitor. The inhibition of differentiation by SB was demonstrated by a reduction of CD14 expression and by a decrease in OZP-activated ROS production. These results indicated that p38 MAPK pathway is involved in 5-LPO inhibitors-dependent potentiation of VD3-induced monocytic differentiation.

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Acknowledgments

This work was supported by Grant Agency of the Czech Republic, grants no. 524/06/P345 and 301/07/1557 and by the Academy of Sciences of the Czech Republic, grants no. 1QS500040507, AVOZ50040507, and AVOZ50040702. The authors wish to thank to Jaromíra Netíková, Iva Lišková, Lenka Vystrčilová, and Martina Urbánková for an excelent technical assistance. The authors are also grateful to Taisia Zatsepin for English correction.

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  1. Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65, Brno, Czech Republic

    Lenka Stixová, Jiřina Procházková, Karel Souček, Jiřina Hofmanová & Alois Kozubík

  2. Department of Animal Physiology and Immunology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic

    Jiřina Procházková

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  1. Lenka Stixová
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Stixová, L., Procházková, J., Souček, K. et al. 5-Lipoxygenase inhibitors potentiate 1α,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway. Mol Cell Biochem 330, 229–238 (2009). https://doi.org/10.1007/s11010-009-0138-x

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