Document Detail


Murine J774 macrophages recognize LPS/IFN-g, non-CpG DNA or two-CpG DNA-containing sequences as immunologically distinct.
MedLine Citation:
PMID:  20097302     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Specific bacterial lipopolysaccharides (LPS), IFN-gamma, and unmethylated cytosine or guanosine-phosphorothioate containing DNAs (CpG) activate host immunity, influencing infectious responses. Macrophages detect, inactivate and destroy infectious particles, and synthetic CpG sequences invoke similar responses of the innate immune system. Previously, murine macrophage J774 cells treated with CpG induced the expression of nitric oxide synthase 2 (NOS2) and cyclo-oxygenase 2 (COX2) mRNA and protein. In this study murine J774 macrophages were exposed to vehicle, interferon gamma+lipopolysaccharide (IFN-g/LPS), non-CpG (SAK1), or two-CpG sequence-containing DNA (SAK2) for 0-18h and gene expression changes measured. A large number of immunostimulatory and inflammatory changes were observed. SAK2 was a stronger activator of TNFalpha- and chemokine expression-related changes than LPS/IFN-g. Up regulation included tumor necrosis factor receptor superfamily genes (TNFRSF's), IL-1 receptor signaling via stress-activated protein kinase (SAPK), NF-kappaB activation, hemopoietic maturation factors and sonic hedgehog/wingless integration site (SHH/Wnt) pathway genes. Genes of the TGF-beta pathway were down regulated. In contrast, LPS/IFN-g-treated cells showed increased levels for TGF-beta signaling genes, which may be linked to the observed up regulation of numerous collagens and down regulation of Wnt pathway genes. SAK1 produced distinct changes from LPS/IFN-g or SAK2. Therefore, J774 macrophages recognize LPS/IFN-g, non-CpG DNA or two-CpG DNA-containing sequences as immunologically distinct.
Authors:
Lynn Crosby; Warren Casey; Kevin Morgan; Hong Ni; Lawrence Yoon; Marilyn Easton; Mary Misukonis; Gary Burleson; Dipak K Ghosh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-01-25
Journal Detail:
Title:  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society     Volume:  22     ISSN:  1089-8611     ISO Abbreviation:  Nitric Oxide     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-01     Completed Date:  2010-07-19     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  9709307     Medline TA:  Nitric Oxide     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-57     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
University of Tennessee Health Sciences Center, Department of Physiology, Memphis, TN 38163, USA. lcrosby@uthsc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cluster Analysis
CpG Islands / immunology*
DNA / immunology*
Immunohistochemistry
Interferon-gamma / immunology*
Lipopolysaccharides / immunology*
Macrophages / cytology,  immunology*
Mice
Nucleotides / immunology*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
AR-43876/AR/NIAMS NIH HHS; AR-47920/AR/NIAMS NIH HHS; AR-48182/AR/NIAMS NIH HHS; R01 AR048182-02/AR/NIAMS NIH HHS; R03 AR047920-01/AR/NIAMS NIH HHS; R29 AR043876-03/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 0/Nucleotides; 82115-62-6/Interferon-gamma; 9007-49-2/DNA
Comments/Corrections

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