| Macrophage Colony Stimulating Factor Regulation by Nuclear Factor Kappa B: A Relevant Pathway in Human Immunodeficiency Virus Type 1 Infected Macrophages. | |
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MedLine Citation:
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PMID: 21895511 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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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Authors:
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Michael Kogan; Valerie Haine; Yuxong Ke; Brian Wigdahl; Tracy Fischer-Smith; Jay Rappaport |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-6 |
Journal Detail:
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Title: DNA and cell biology Volume: - ISSN: 1557-7430 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9004522 Medline TA: DNA Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University , Philadelphia, Pennsylvania. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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