Journal article
Macrophage Colony Stimulating Factor Regulation by Nuclear Factor Kappa B: A Relevant Pathway in Human Immunodeficiency Virus Type 1 Infected Macrophages
DNA and cell biology, v 31(3), pp 28-289
01 Mar 2012
PMID: 21895511
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Macrophage colony stimulating factor (M-CSF) is a cytokine that promotes monocyte differentiation and survival. When overexpressed, M-CSF contributes to pathology in a wide variety of diseases, including osteoporosis, obesity, certain human cancers, and in human immunodeficiency virus type 1 (HIV-1) infection, particularly with respect to monocyte/macrophage infection and the development of HIV-1 associated central nervous system disorders. In this study, our aim was to expand the current knowledge of M-CSF regulation, focusing on nuclear factor kappa B (NF-κB), a transcription factor playing a prominent role during inflammation and HIV-1 infection. Our results suggest that tumor necrosis factor alpha (TNF-α) promotes M-CSF secretion in primary macrophages and activates the −1310/+48 bp M-CSF promoter in Mono-Mac 1 cells. Inhibitors of the NF-κB pathway diminish this response. We identified four putative NF-κB and four CCAAT-enhancer-binding protein beta binding sites within the
M-CSF
promoter. Our findings, using promoter constructs mutated at individual NF-κB sites within the
M-CSF
promoter region, suggest that these sites are redundant with respect to NF-κB regulation. TNF-α treatment promoted NF-κB p65 binding to the
M-CSF
promoter in phorbol 12-myristate 13-acetate (PMA) treated U937 cells chronically infected with HIV-1 (U1 cells), but not in PMA treated uninfected U937 cells, suggesting that the presence of HIV-1 increases the NF-κB response. In conclusion, our findings demonstrate that NF-κB induces
M-CSF
expression on a promoter level via multiple functional NF-κB binding sites and that this pathway is likely relevant in HIV-1 infection of macrophages.
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Details
- Title
- Macrophage Colony Stimulating Factor Regulation by Nuclear Factor Kappa B: A Relevant Pathway in Human Immunodeficiency Virus Type 1 Infected Macrophages
- Creators
- Michael Kogan - 1Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, Philadelphia, PennsylvaniaValerie Haine - 1Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, Philadelphia, PennsylvaniaYuxong Ke - 1Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, Philadelphia, PennsylvaniaBrian Wigdahl - 2Department of Microbiology and Immunology and Center for Molecular Virology and Translational Hemoscience, Drexel University College of Medicine, Philadelphia, PennsylvaniaTracy Fischer-Smith - 1Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, Philadelphia, PennsylvaniaJay Rappaport - 1Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, Philadelphia, Pennsylvania
- Publication Details
- DNA and cell biology, v 31(3), pp 28-289
- Publisher
- Mary Ann Liebert, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000301358100006
- Scopus ID
- 2-s2.0-84858114626
- Other Identifier
- 991014877976604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity