Neutrophil signaling pathways activated by bacterial DNA stimulation

We have previously shown that bacterial DNA activates human neutrophils in a CpG-independent manner. In this study, we have characterized the signaling pathways involved in the activation mechanism. We found that p38 MAPK, ERK1/2, and JNK pathways, as well as the PI3K/Akt pathway, are activated by b...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Costas, Mónica Alejandra, Coso, Omar Adrian, Gamberale, Romina, Vermeulen, Mónica, Salamone, Gabriela V., Tanos, Tamara, Trevani, Analía S.
Publicado: 2006
Materias:
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v177_n6_p4037_Alvarez
http://hdl.handle.net/20.500.12110/paper_00221767_v177_n6_p4037_Alvarez
Aporte de:
Descripción
Sumario:We have previously shown that bacterial DNA activates human neutrophils in a CpG-independent manner. In this study, we have characterized the signaling pathways involved in the activation mechanism. We found that p38 MAPK, ERK1/2, and JNK pathways, as well as the PI3K/Akt pathway, are activated by bacterial DNA. We also determined that bacterial DNA induces NF-κB and AP-1 activation. When analyzing the role of these pathways on neutrophil functions, we observed that up-regulation of CD11b triggered by bacterial DNA was decreased by pharmacological inhibitors of the p38 MAPK, ERK1/2, and JNK, whereas stimulation of IL-8 release was dependent on p38, ERK1/2, and NF-κB. Moreover, we found that IL-8 production was markedly enhanced by inhibition of JNK, suggesting that this pathway negatively modulates NF-κB-dependent transcription. We also observed that bacterial DNA stimulated IL-1R-associated kinase-1 kinase activity and its partial degradation. Finally, we determined that bacterial DNA stimulated CD11b up-regulation in TLR9 -/- but not in MyD88 -/- mouse neutrophils, supporting that bacterial DNA induces neutrophil activation through a TLR9-independent and MyD88-dependent pathway. Copyright © 2006 by The American Association of Immunologists, Inc.