Document Detail


Pharmacologic augmentation of hypoxia-inducible factor-1alpha with mimosine boosts the bactericidal capacity of phagocytes.
MedLine Citation:
PMID:  18173364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia-inducible factor (HIF)-1alpha is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF-1alpha agonist mimosine can boost the capacity of human phagocytes and whole blood to kill the leading pathogen Staphylococcus aureus in a dose-dependent fashion and reduce the lesion size in a murine model of S. aureus skin infection. This provides the first proof of principle for a novel approach to the treatment of bacterial infection by pharmacologically augmenting the host phagocytic function.
Authors:
Annelies S Zinkernagel; Carole Peyssonnaux; Randall S Johnson; Victor Nizet
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  197     ISSN:  0022-1899     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-15     Completed Date:  2008-02-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  214-7     Citation Subset:  AIM; IM    
Affiliation:
1Division of Pediatric Pharmacology and Drug Discovery, School of Medicine, University of California, San Diego, La Jolla 92093-0687, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Bactericidal Activity
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / agonists*,  immunology*
Immunity, Innate
Mice
Mice, Inbred C57BL
Mimosine / pharmacology*
Monocytes / immunology
Neutrophils / immunology
Phagocytes / immunology
Respiratory Burst
Staphylococcal Infections / drug therapy,  immunology,  microbiology
Staphylococcal Skin Infections / drug therapy*,  immunology*,  microbiology
Staphylococcus aureus / drug effects*,  pathogenicity
U937 Cells
Grant Support
ID/Acronym/Agency:
AI060840/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1, alpha Subunit; 500-44-7/Mimosine

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