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:  MEDLINE    
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; Research Support, N.I.H., Extramural     Date:  2011-09-06
Journal Detail:
Title:  DNA and cell biology     Volume:  31     ISSN:  1557-7430     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-12     Completed Date:  2012-04-19     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  280-9     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Gene Expression Regulation*
HIV-1*
Humans
Macrophage Colony-Stimulating Factor / genetics*
Macrophages / metabolism*,  virology
NF-kappa B / metabolism*
Promoter Regions, Genetic
Grant Support
ID/Acronym/Agency:
DA019807/DA/NIDA NIH HHS; MH090910/MH/NIMH NIH HHS; NS032092/NS/NINDS NIH HHS; NS047031/NS/NINDS NIH HHS; T32MH079785/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B; 81627-83-0/Macrophage Colony-Stimulating Factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Escaping the cut by restriction enzymes through single-strand self-annealing of host-edited 12-bp an...
Next Document:  The Association Between Maternal Alcohol Use and Smoking in Early Pregnancy and Congenital Cardiac D...