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

Author： Stixová Lenka Procházková Jiřina Souček Karel Hofmanová Jiřina Kozubík Alois

Publisher： Springer Publishing Company

ISSN： 0300-8177

Source： Molecular and Cellular Biochemistry, Vol.330, Iss.1-2, 2009-10, pp. : 229-238

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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.