Involvement of mitogen-activated protein kinases in Group B Streptococcus-induced macrophage apoptosis.
We previously demonstrated that Group B Streptococcus (GBS), a pathogen that causes serious neonatal infections, induces macrophage apoptosis by beta-hemolysin to avoid the host immune response. GBS-induced macrophage apoptosis is characterized by a calcium increase and is caspase-independent. This study reports the involvement of c-Jun NH(2)-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (ERK), three members of mitogen-activated protein kinases (MAPKs) family, in GBS-induced macrophage apoptosis. Our data indicate that during induction of apoptosis live GBS stimulates a strong persistent activation of JNK and p38 with concomitant inhibition of ERK. The time courses of MAPKs activation strongly correlate with GBS-induced macrophage apoptosis and are macrophage:GBS ratio-dependent. In fact, when GBS does not cause macrophage apoptosis, e.g. low macrophage:GBS ratio or non hemolytic GBS (gGBS), it induces a transient activation of JNK, p38, and ERK MAPKs. These latter results indicate that sustained and persistent activation of JNK and p38 and inhibition of ERK are involved in the GBS-induced macrophage apoptotic process and suggest that the time course and balance of MAPKs activation are critical for different macrophage responses to GBS (apoptosis versus antimicrobicidal activity). This study indicates a correlation between MAPKs activation and GBS-induced macrophage apoptosis. However, since neither ERK nor p38 inhibitors had an effect on GBS-induced apoptosis, their role in the complex signal network leading to GBS-induced macrophage apoptosis remains to be defined.
Fettucciari
Katia
K
Department of Clinical and Experimental Medicine, General Pathology and Immunology Section, University of Perugia, General Hospital--Monteluce, Perugia 06100, Italy.
Fetriconi
Ilaria
I
Bartoli
Andrea
A
Rossi
Ruggero
R
Marconi
Pierfrancesco
P
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004789:Enzyme Activation; D005260:Female; D005419:Flavonoids / Q000378:metabolism; D005434:Flow Cytometry; D007093:Imidazoles / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000502:physiology; D008297:Male; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D013292:Streptococcus agalactiae / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one