PMID- 17182557
OWN - NLM
STAT- MEDLINE
DCOM- 20070306
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 1
DP  - 2007 Jan 1
TI  - IFN-gamma negatively regulates CpG-induced IL-10 in bone marrow-derived dendritic 
      cells.
PG  - 211-8
AB  - Dendritic cells (DCs) are important players in the regulation of Th1- and 
      Th2-dominated immune responses. In these studies we showed that IFN-gamma, the 
      key mediator of Th1 immunity, actively suppressed the production of IL-10 in 
      murine DCs when activated with LPS or CpG. Our analysis revealed that both LPS 
      and CpG induced IL-10 and IL-12 production but that the presence of IFN-gamma, in 
      a dose-dependent manner, suppressed the production of IL-10 while enhancing that 
      of IL-12. The observed inhibition of IL-10 production was independent of IL-12. 
      Experiments performed with STAT-1 knockout mice demonstrated that the primary 
      production of IL-12 induced by CpG was STAT-1 dependent, whereas the production 
      of IL-10 was not. This finding was confirmed by the observation that CpG-induced 
      IL-12 production could be inhibited by anti-IFN-beta Abs, whereas CpG-induced 
      IL-10 production could not be inhibited. These data also demonstrated that the 
      inhibitory effect of IFN-gamma on IL-10 expression was STAT-1 dependent and 
      transcriptionally regulated. Thus, DCs respond to CpG by producing 
      proinflammatory and anti-inflammatory cytokines such as IL-12 and IL-10, 
      respectively, and IFN-gamma acts to not only enhance IL-12 but also to inhibit 
      IL-10 production. The current data demonstrate a novel pathway for 
      IFN-gamma-mediated immunoregulation and suggest that IFN-gamma-dependent 
      suppression of IL-10 production by DCs may be involved in the antagonism between 
      Th1 and Th2 patterns of immune reactivity.
FAU - Flores, Rafael R
AU  - Flores RR
AD  - Department of Immunology and Department of Medicine, University of Pittsburgh, 
      Pittsburgh, PA 15261, USA.
FAU - Diggs, Kelly A
AU  - Diggs KA
FAU - Tait, Lauren M
AU  - Tait LM
FAU - Morel, Penelope A
AU  - Morel PA
LA  - eng
GR  - P01 CA073743/CA/NCI NIH HHS/United States
GR  - CA73743/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Toll-Like Receptors)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Bone Marrow/immunology
MH  - Dendritic Cells/*drug effects/immunology
MH  - Interferon-gamma/*pharmacology/physiology
MH  - Interleukin-10/*antagonists & inhibitors/genetics/metabolism
MH  - Interleukin-12/genetics/metabolism
MH  - Ligands
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Oligodeoxyribonucleotides/pharmacology
MH  - STAT1 Transcription Factor/genetics/*metabolism
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
MH  - Toll-Like Receptors/agonists
MH  - Transcription, Genetic/drug effects
EDAT- 2006/12/22 09:00
MHDA- 2007/03/07 09:00
CRDT- 2006/12/22 09:00
PHST- 2006/12/22 09:00 [pubmed]
PHST- 2007/03/07 09:00 [medline]
PHST- 2006/12/22 09:00 [entrez]
AID - 178/1/211 [pii]
AID - 10.4049/jimmunol.178.1.211 [doi]
PST - ppublish
SO  - J Immunol. 2007 Jan 1;178(1):211-8. doi: 10.4049/jimmunol.178.1.211.