Trypanosoma brucei brucei induces interferon-gamma expression in rat dorsal root ganglia cells via a tyrosine kinase-dependent pathway.
Dorsal root ganglia (DRG) were shown to express neuronal interferon (IFN)-gamma, which supports Trypanosoma brucei brucei growth. The ability of a trypanosome-derived factor (TLTF) to activate DRG to neuronal IFN-gamma secretion was investigated, together with the signaling pathway that might be involved during this process. Immunohistochemical staining revealed expression of neuronal IFN-gamma on stimulation with TLTF, which was blocked with the tyrosine protein-kinase inhibitor, tyrphostin A47. Western blot was used to analyze DRG lysates prepared at different time points after stimulation with TLTF. A tyrosine-phosphorylated protein induced at 15 min was seen as a band of 120-150 kDa, followed by a decrease to control levels after 30 min. A47 greatly suppressed the TLTF-induced tyrosine protein kinase activity. In addition, evidence suggesting that the transcription factor STAT-1 may play a key role in the TLTF signaling pathway was provided by the blocking effects of A47 on STAT-1 translocation to the nucleus.
Eltayeb
R
R
Division of Infectious Diseases, Karolinska Institute, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
Sharafeldin
A
A
Jaster
R
R
Bittorf
T
T
Mix
E
E
Bakhiet
M
M
D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015800:Protozoan Proteins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D020032:Tyrphostins / Q000494:pharmacology
D015800:Protozoan Proteins; C107172:T lymphocyte triggering factor, Trypanosoma brucei; D020032:Tyrphostins; C060152:tyrphostin 47; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases