Publication Date:
2002-08-31
Description:
The bacterium Bacillus anthracis causes the death of macrophages, which may allow it to avoid detection by the innate immune system. We found that B. anthracis lethal factor (LF) selectively induces apoptosis of activated macrophages by cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK) kinases (MKKs) that activate p38 MAPKs. Because macrophages that are deficient in transcription factor nuclear factor kappaB (NF-kappaB) are also sensitive to activation-induced death and p38 is required for expression of certain NF-kappaB target genes, p38 is probably essential for synergistic induction of those NF-kappaB target genes that prevent apoptosis of activated macrophages. This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Jin Mo -- Greten, Florian R -- Li, Zhi-Wei -- Karin, Michael -- AI43477/AI/NIAID NIH HHS/ -- ES04151/ES/NIEHS NIH HHS/ -- ES06376/ES/NIEHS NIH HHS/ -- ES10337/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):2048-51. Epub 2002 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12202685" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Antigens, Bacterial
;
*Apoptosis
;
Bacterial Toxins/*toxicity
;
Calcium-Calmodulin-Dependent Protein Kinases/genetics/metabolism
;
Carrier Proteins/*toxicity
;
Cell Line
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Gene Expression
;
I-kappa B Kinase
;
Imidazoles/pharmacology
;
Lipopolysaccharides/pharmacology
;
MAP Kinase Kinase 3
;
MAP Kinase Kinase 6
;
MAP Kinase Signaling System
;
Macrophage Activation
;
Macrophages/enzymology/immunology/*physiology
;
Mice
;
Mice, Inbred C57BL
;
Mitogen-Activated Protein Kinase Kinases/genetics/metabolism
;
Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
;
NF-kappa B/genetics/metabolism
;
Necrosis
;
Protein-Serine-Threonine Kinases/genetics/metabolism
;
Protein-Tyrosine Kinases/genetics/metabolism
;
Pyridines/pharmacology
;
Teichoic Acids/pharmacology
;
Transcription Factor RelA
;
p38 Mitogen-Activated Protein Kinases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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