Abstract
Interleukin (IL)-8 serves as a major chemoattractant for neutrophils and has also been proposed to affect cancer progression. In the present study, we show that IGF-I stimulates IL-8 mRNA expression and IL-8 secretion in the leukemic cell line HL-60. Stimulation of IL-8 expression was completely attenuated by two inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK), which phosphorylates the MAPKs extracellular-regulated kinase (ERK)1 and ERK2, and by the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. In contrast, inhibitors of p38 MAPK and phosphatidylinositol-3 kinase (PI3K) did not abrogate the effect of IGF-I. We also show that IGF-I stimulates the activation of ERK1 and ERK2, but we could not detect any effect of IGF-I on the phosphorylation of p38, JNK(p46) or JNK(p54). Collectively, our results suggest that basal JNK activity and activation of the MEK-ERK pathway are required for upregulation of IL-8 by IGF-I in HL-60 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Anthracenes / pharmacology
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Apoptosis / drug effects
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Butadienes / pharmacology
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Cell Survival / drug effects
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Chromones / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Gene Expression Regulation, Leukemic / drug effects
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HL-60 Cells
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Humans
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Hydrogen Peroxide / pharmacology
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Imidazoles / pharmacology
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Insulin-Like Growth Factor I / pharmacology*
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Insulin-Like Growth Factor I / physiology
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Interleukin-8 / genetics
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Interleukin-8 / metabolism*
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JNK Mitogen-Activated Protein Kinases
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Kinetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism*
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Morpholines / pharmacology
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Nitriles / pharmacology
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Oxazoles / pharmacology
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Phosphorylation / drug effects
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Pyridines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, IGF Type 1 / antagonists & inhibitors
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Wortmannin
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p38 Mitogen-Activated Protein Kinases
Substances
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2-methyl-4-phenyl-(4-pyridyl)oxazole
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Androstadienes
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Anthracenes
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Butadienes
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Interleukin-8
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Morpholines
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Nitriles
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Oxazoles
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Pyridines
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RNA, Messenger
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U 0126
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pyrazolanthrone
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Insulin-Like Growth Factor I
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Hydrogen Peroxide
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Receptor, IGF Type 1
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Wortmannin