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Identification and characterization of Chlamydia pneumoniae-specific proteins that activate tumor necrosis factor alpha production in RAW 264.7 murine macrophages
- Source :
- Infection and immunity. 76(4)
- Publication Year :
- 2008
-
Abstract
- Chlamydia pneumoniaeis a common respiratory pathogen, which activates macrophages to induce inflammatory cytokines that may promote atherosclerosis. However, the antigens that induce macrophage activation have not been well defined. In the current study, three chlamydial proteins which are recognized during human infection, outer membrane protein 2 (OMP2) and two 53-kDa proteins (Cpn 0980 and Cpn 0809), were investigated to determine whether they activate macrophages and, if they do, what mechanism they use for this activation. It was shown that these three proteins could (i) induce expression of tumor necrosis factor alpha (TNF-α) and tissue factor and (ii) induce phosphorylation of p44/42 mitogen-activated protein kinases (MAPK) and activation of early growth response factor 1 (Egr-1). Control proteins, the N-terminal fragment of polymorphic membrane protein 8 and the thioredoxin portion of the fusion protein, had no effect on macrophages. Treatment of cells with a MEK1/2 inhibitor, U0126, dramatically reduced the phosphorylation of ERK, activation of Egr-1, and expression of TNF-α in macrophages treated with recombinant proteins. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the MAPK pathway. Chlamydial protein-induced expression of TNF-α was significantly reduced in macrophages lacking TLR2 or TLR4. These findings suggest thatC. pneumoniaemay activate macrophages through OMP2, Cpn 0980, and Cpn 0809 in addition to cHSP60 and that activation occurs via TLR2 or TLR4, Egr-1, and MAPK pathways.
- Subjects :
- MAPK/ERK pathway
medicine.medical_treatment
Immunology
Biology
Microbiology
Proinflammatory cytokine
Cell Line
Thromboplastin
Mice
Bacterial Proteins
medicine
Macrophage
Animals
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Early Growth Response Protein 1
Mitogen-Activated Protein Kinase 1
Host Response and Inflammation
Tumor Necrosis Factor-alpha
Macrophages
Chlamydophila pneumoniae
Molecular biology
Fusion protein
Recombinant Proteins
Infectious Diseases
Cytokine
Membrane protein
Gene Expression Regulation
TLR4
Parasitology
Tumor necrosis factor alpha
Subjects
Details
- ISSN :
- 10985522
- Volume :
- 76
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Infection and immunity
- Accession number :
- edsair.doi.dedup.....effc8de560ea5195f025acea3b878491