title: The regulation of OLFM4 expression in myeloid precursor cells relies on NF-kappaB transcription factor.
abstract: The human olfactomedin 4 gene (OLFM4, also known as hGC-1, GW112) is thought to be a useful marker for early myeloid development. To understand the molecular mechanisms underlying granulocyte colony-stimulating factor (G-CSF)-stimulated OLFM4 expression, we characterized the promoter region of OLFM4. The 35-bp region (-101 to -66) of the proximal promoter regulated reporter gene expression, and mutation of the nuclear factor (NF)-kappaB binding site within the promoter abolished the binding of the transcription factor and the ability to regulate OLFM4 expression. G-CSF increased reactive oxygen species (ROS) production in human CD34(+) cells, which was abrogated by inhibition of phosphatidylinositol 3-kinase (PI3K) or NADPH oxidase. Phosphorylation of ERK1/2 mitogen-activated protein kinase (MAPK) induced by G-CSF inhibited by the antioxidant N-acetyl-L-cysteine (NAC), ERK1/2 inhibitor PD98059, or U0126. However, phosphorylation of signal transducer and activator of transcription (STAT)3 was only partially inhibited by NAC, but not by PD98059 or U0126. Inhibition of the ERK pathway remarkably decreased OLFM4 expression and this inhibition required NF-kappaB transcription factor. Inhibition of ROS or the ERK pathway remarkably decreased G-CSF-induced OLFM4 expression. Our results suggest that G-CSF-induced expression of OLFM4 is regulated by the transcription factor NF-kappaB, and that this induction is mediated by the ERK1/2 MAPK signaling pathway through PI3K-driven ROS production.
authors.affiliation: Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Kyung L
authors.initials: KL
authors.lastname: Chin
authors.forename: Wulin
authors.initials: W
authors.lastname: Aerbajinai
authors.forename: Jiangqiong
authors.initials: J
authors.lastname: Zhu
authors.forename: LaShawn
authors.initials: L
authors.lastname: Drew
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Wenli
authors.initials: W
authors.lastname: Liu
authors.forename: Griffin P
authors.initials: GP
authors.lastname: Rodgers