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Publication : GM-CSF enhances a CpG-independent pathway of neutrophil activation triggered by bacterial DNA.

First Author  Fuxman Bass JI Year  2008
Journal  Mol Immunol Volume  46
Issue  1 Pages  37-44
PubMed ID  18701168 Mgi Jnum  J:140587
Mgi Id  MGI:3814134 Doi  10.1016/j.molimm.2008.06.033
Citation  Bass JI, et al. (2008) GM-CSF enhances a CpG-independent pathway of neutrophil activation triggered by bacterial DNA. Mol Immunol 46(1):37-44
abstractText  We have previously demonstrated that bacterial DNA induces neutrophil activation through a CpG- and TLR9-independent but MyD88-dependent-pathway. In this study we determined that GM-CSF enhances the activation of neutrophils by bacterial DNA. Granulocyte-macrophage colony-stimulating factor increased IL-8 and IL-1beta secretion, and CD11b-upregulation induced by single-stranded bacterial DNA. It also enhanced neutrophil IL-8 production induced by double-stranded bacterial DNA, methylated single-stranded DNA, plasmid DNA, and phosphorothioated-CpG and non-CpG-oligodeoxynucleotides. Together these observations indicated that GM-CSF enhances neutrophil responses triggered by bacterial DNA in a CpG-independent fashion. We also found that GM-CSF enhanced the activation of the MAPKs p38 and ERK1/2 induced by bacterial DNA. Moreover, the pharmacological inhibition of these pathways significantly diminished GM-CSF ability to increase neutrophil activation by bacterial DNA. Finally, we observed that GM-CSF was unable to increase the activation of MyD88(-/-) neutrophils by bacterial DNA. Our findings suggest that GM-CSF modulates the CpG-independent, MyD88-dependent neutrophil response to bacterial DNA, by increasing the activation of the MAPKs p38 and ERK1/2.
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