Protein kinase Cepsilon is required for macrophage activation and defense against bacterial infection.
J Exp Med
; 194(9): 1231-42, 2001 Nov 05.
Article
in En
| MEDLINE
| ID: mdl-11696589
ABSTRACT
To assess directly the role of protein kinase C (PKC)epsilon in the immune system, we generated mice that carried a homozygous disruption of the PKCepsilon locus. PKCepsilon(-/-) animals appeared normal and were generally healthy, although female mice frequently developed a bacterial infection of the uterus. Macrophages from PKCepsilon(-/-) animals demonstrated a severely attenuated response to lipopolysaccharide (LPS) and interferon (IFN)gamma, characterized by a dramatic reduction in the generation of NO, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. Further analysis revealed that LPS-stimulated macrophages from PKCepsilon(-/-) mice were deficient in the induction of nitric oxide synthase (NOS)-2, demonstrating a decrease in the activation of IkappaB kinase, a reduction in IkappaB degradation, and a decrease in nuclear factor (NF)kappaB nuclear translocation. After intravenous administration of Gram-negative or Gram-positive bacteria, PKCepsilon(-/-) mice demonstrated a significantly decreased period of survival. This study provides direct evidence that PKCepsilon is critically involved at an early stage of LPS-mediated signaling in activated macrophages. Furthermore, we demonstrate that in the absence of PKCepsilon, host defense against bacterial infection is severely compromised, resulting in an increased incidence of mortality.
Full text:
1
Collection:
01-internacional
Health context:
2_ODS3
/
3_ND
Database:
MEDLINE
Main subject:
Staphylococcal Infections
/
Protein Kinase C
/
Escherichia coli Infections
/
Isoenzymes
/
Macrophage Activation
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2001
Document type:
Article