Document Detail


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