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- Title
GM-CSF Priming Drives Bone Marrow-Derived Macrophages to a Pro-Inflammatory Pattern and Downmodulates PGE<sub>2</sub> in Response to TLR2 Ligands.
- Authors
Sorgi, Carlos Arterio; Rose, Stephanie; Court, Nathalie; Carlos, Daniela; Garcia Paula-Silva, Francisco Wanderley; Assis, Patricia Aparecida; Frantz, Fabiani Gai; Ryffel, Bernhard; Quesniaux, Valerie; Faccioli, Lúcia Helena
- Abstract
In response to pathogen recognition by Toll-like receptors (TLRs) on their cell surface, macrophages release lipid mediators and cytokines that are widely distributed throughout the body and play essential roles in host responses. Granulocyte macrophage colony-stimulating factor (GM-CSF) is important for the immune response during infections to improve the clearance of microorganisms. In this study, we examined the release of mediators in response to TLR2 ligands by bone marrow-derived macrophages (BMDMs) primed with GM-CSF. We demonstrated that when stimulated with TLR2 ligands, non-primed BMDMs preferentially produced PGE2 in greater amounts than LTB4. However, GM-CSF priming shifted the release of lipid mediators by BMDMs, resulting in a significant decrease of PGE2 production in response to the same stimuli. The decrease of PGE2 production from primed BMDMs was accompanied by a decrease in PGE-synthase mRNA expression and an increase in TNF-α and nitric oxide (NO) production. Moreover, some GM-CSF effects were potentiated by the addition of IFN-γ. Using a variety of TLR2 ligands, we established that PGE2 release by GM-CSF-primed BMDMs was dependent on TLR2 co-receptors (TLR1, TLR6), CD14, MyD88 and the nuclear translocation of NFkB but was not dependent on peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. Indeed, GM-CSF priming enhanced TLR2, TLR4 and MyD88 mRNA expression and phospho-IkBa formation. These findings demonstrate that GM-CSF drives BMDMs to present a profile relevant to the host during infections.
- Subjects
GRANULOCYTE-macrophage colony-stimulating factor; BONE marrow; IMMUNE system; KILLER cells; CYTOKINES; IMMUNOREGULATION; IMMUNE response
- Publication
PLoS ONE, 2012, Vol 7, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0040523