PMID- 22808181
OWN - NLM
STAT- MEDLINE
DCOM- 20130319
LR  - 20220318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - GM-CSF priming drives bone marrow-derived macrophages to a pro-inflammatory 
      pattern and downmodulates PGE2 in response to TLR2 ligands.
PG  - e40523
LID - 10.1371/journal.pone.0040523 [doi]
LID - e40523
AB  - 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 
      PGE(2) in greater amounts than LTB(4). However, GM-CSF priming shifted the 
      release of lipid mediators by BMDMs, resulting in a significant decrease of 
      PGE(2) production in response to the same stimuli. The decrease of PGE(2) 
      production from primed BMDMs was accompanied by a decrease in PGE-synthase mRNA 
      expression and an increase in TNF-alpha and nitric oxide (NO) production. Moreover, 
      some GM-CSF effects were potentiated by the addition of IFN-gamma. Using a variety of 
      TLR2 ligands, we established that PGE(2) release by GM-CSF-primed BMDMs was 
      dependent on TLR2 co-receptors (TLR1, TLR6), CD14, MyD88 and the nuclear 
      translocation of NFkappaB but was not dependent on peroxisome proliferator-activated 
      receptor-gamma (PPAR-gamma) activation. Indeed, GM-CSF priming enhanced TLR2, TLR4 and 
      MyD88 mRNA expression and phospho-IkappaBalpha formation. These findings demonstrate that 
      GM-CSF drives BMDMs to present a profile relevant to the host during infections.
FAU - Sorgi, Carlos Arterio
AU  - Sorgi CA
AD  - Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de 
      Ciencias Farmaceuticas de Ribeirao Preto - Universidade de Sao Paulo - Ribeirao 
      Preto, SP, Brazil.
FAU - Rose, Stephanie
AU  - Rose S
FAU - Court, Nathalie
AU  - Court N
FAU - Carlos, Daniela
AU  - Carlos D
FAU - Paula-Silva, Francisco Wanderley Garcia
AU  - Paula-Silva FW
FAU - Assis, Patricia Aparecida
AU  - Assis PA
FAU - Frantz, Fabiani Gai
AU  - Frantz FG
FAU - Ryffel, Bernhard
AU  - Ryffel B
FAU - Quesniaux, Valerie
AU  - Quesniaux V
FAU - Faccioli, Lucia Helena
AU  - Faccioli LH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120713
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Ligands)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Bacteria/metabolism
MH  - Dinoprostone/*metabolism
MH  - Down-Regulation/*drug effects
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Inflammation/metabolism/*pathology
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-10/biosynthesis
MH  - Leukotriene B4/metabolism
MH  - Ligands
MH  - Lipid Metabolism
MH  - Macrophages/drug effects/metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - PPAR gamma/metabolism
MH  - Protein Transport/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Toll-Like Receptor 2/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3396658
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/07/19 06:00
MHDA- 2013/03/21 06:00
PMCR- 2012/07/13
CRDT- 2012/07/19 06:00
PHST- 2011/07/20 00:00 [received]
PHST- 2012/06/12 00:00 [accepted]
PHST- 2012/07/19 06:00 [entrez]
PHST- 2012/07/19 06:00 [pubmed]
PHST- 2013/03/21 06:00 [medline]
PHST- 2012/07/13 00:00 [pmc-release]
AID - PONE-D-11-13804 [pii]
AID - 10.1371/journal.pone.0040523 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e40523. doi: 10.1371/journal.pone.0040523. Epub 2012 Jul 13.