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.

• MeSH
• Arachidonate 5-Lipoxygenase genetics   MeSH
• Benzoquinones pharmacology   MeSH
• Cell Differentiation drug effects   MeSH
• HL-60 Cells MeSH
• Indoles pharmacology   MeSH
• Lipoxygenase Inhibitors pharmacology   MeSH
• Humans MeSH
• p38 Mitogen-Activated Protein Kinases metabolism   MeSH
• Monocytes cytology   MeSH
• Vitamin D analogs & derivatives   pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone MeSH Browser
• Arachidonate 5-Lipoxygenase MeSH
• Benzoquinones MeSH
• dihydroxy-vitamin D3 MeSH Browser
• Indoles MeSH
• Lipoxygenase Inhibitors MeSH
• p38 Mitogen-Activated Protein Kinases MeSH
• MK-886 MeSH Browser
• Vitamin D MeSH