| First Author | Alvarez ME | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 6 | Pages | 4037-46 |
| PubMed ID | 16951367 | Mgi Jnum | J:138045 |
| Mgi Id | MGI:3804112 | Doi | 10.4049/jimmunol.177.6.4037 |
| Citation | Alvarez ME, et al. (2006) Neutrophil signaling pathways activated by bacterial DNA stimulation. J Immunol 177(6):4037-46 |
| abstractText | 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-kappaB 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-kappaB. Moreover, we found that IL-8 production was markedly enhanced by inhibition of JNK, suggesting that this pathway negatively modulates NF-kappaB-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. |
