Back to Search
Start Over
Activation of transcription factors AP-1 and NF-kappa B in murine Chagasic myocarditis.
- Source :
-
Infection and immunity [Infect Immun] 2003 May; Vol. 71 (5), pp. 2859-67. - Publication Year :
- 2003
-
Abstract
- The myocardium of CD1 mice was examined for the activation of signal transduction pathways leading to cardiac inflammation and subsequent remodeling during Trypanosoma cruzi infection (Brazil strain). The activity of three pathways of the mitogen-activated protein kinases (MAPKs) was determined. Immunoblotting revealed a persistent elevation of phosphorylated (activated) extracellular-signal-regulated kinase (ERK), which regulates cell proliferation. During infection there was a transient activation of p38 MAPK but no activation of Jun N-terminal kinase. Early targets of activated ERK, c-Jun and c-Fos, were elevated during infection, as demonstrated by semiquantitative reverse transcription-PCR. Immunostaining revealed that the endothelium and the interstitial cells were most intensely stained with antibodies to c-Jun and c-Fos. Soon after infection, AP-1 and NF-kappa B DNA binding activity was increased. Protein levels of cyclin D1, the downstream target of ERK and NF-kappa B, were induced during acute infection. Immunostaining demonstrated increased expression of cyclin D1 in the vascular and endocardial endothelium, inflammatory cells, and the interstitial areas. Increased expression of the cyclin D1-specific phosphorylated retinoblastoma protein (Ser780) was also evident. Immunoblotting and immunostaining also demonstrated increased expression of proliferating cellular nuclear antigen that was predominantly present in the inflammatory cells, interstitial areas (i.e., fibroblasts), and endothelium. These data demonstrate that T. cruzi infection results in activation of the ERK-AP-1 pathway and NF-kappa B. Cyclin D1 expression was also increased. These observations provide a molecular basis for the activation of pathways involved in cardiac remodeling in chagasic cardiomyopathy.
- Subjects :
- Animals
Chagas Cardiomyopathy pathology
Cyclin D1 analysis
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System physiology
Male
Mice
Mitogen-Activated Protein Kinases metabolism
Phosphorylation
Proliferating Cell Nuclear Antigen analysis
Proto-Oncogene Proteins c-jun analysis
Proto-Oncogene Proteins c-jun genetics
Retinoblastoma Protein analysis
Reverse Transcriptase Polymerase Chain Reaction
p38 Mitogen-Activated Protein Kinases
Chagas Cardiomyopathy metabolism
NF-kappa B metabolism
Transcription Factor AP-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0019-9567
- Volume :
- 71
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 12704159
- Full Text :
- https://doi.org/10.1128/IAI.71.5.2859-2867.2003