5-Lipoxygenase inhibitors potentiate 1alpha,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- arachidonát-5-lipoxygenasa genetika MeSH
- benzochinony farmakologie MeSH
- buněčná diferenciace účinky léků MeSH
- HL-60 buňky MeSH
- indoly farmakologie MeSH
- inhibitory lipoxygenas farmakologie MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- monocyty cytologie MeSH
- vitamin D analogy a deriváty farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone MeSH Prohlížeč
- arachidonát-5-lipoxygenasa MeSH
- benzochinony MeSH
- dihydroxy-vitamin D3 MeSH Prohlížeč
- indoly MeSH
- inhibitory lipoxygenas MeSH
- mitogenem aktivované proteinkinasy p38 MeSH
- MK-886 MeSH Prohlížeč
- vitamin D MeSH
The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D(3) (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, 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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