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5 lipoxygenase inhibitors potentiate 1alpha,25 dihydroxyvitamin D3 induced monocytic differentiation by activating p38 MAPK pathway

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STIXOVÁ Lenka PROCHÁZKOVÁ Jiřina SOUČEK Karel HOFMANOVÁ Jiřina KOZUBÍK Alois

Rok publikování 2009
Druh Článek v odborném periodiku
Časopis / Zdroj Mol Cell Biochem
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Genetika a molekulární biologie
Klíčová slova Differentiation; 1alpha25 dihydroxyvitamin D3; 5 lipoxygenase inhibitors; p38 MAPK;
Popis The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D3 (VD3) induces differentiation towards 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, IkappaB 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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