PMID- 10453004
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 5
DP  - 1999 Sep 1
TI  - Lipopolysaccharide induces in macrophages the synthesis of the suppressor of
      cytokine signaling 3 and suppresses signal transduction in response to the
      activating factor IFN-gamma.
PG  - 2640-7
AB  - The goal of this study was to investigate how bacterial LPS affects macrophage
      responsiveness to the activating factor IFN-gamma. Pretreatment of macrophages
      with LPS for <2 h increased the transcriptional response to IFN-gamma. In
      contrast, simultaneous stimulation with IFN-gamma and LPS, or pretreatment with
      LPS for >4 h, suppressed Stat1 tyrosine 701 phosphorylation, dimerization, and
      transcriptional activity in response to IFN-gamma. Consistently, the induction of
      MHCII protein by IFN-gamma was antagonized by LPS pretreatment. Neutralizing Abs 
      to IL-10 were without effect on LPS-mediated suppression of Stat1 activation.
      Decreased IFN-gamma signal transduction after LPS treatment corresponded to a
      direct induction of suppressor of cytokine signaling3 (SOCS3) mRNA and protein.
      Under the same conditions socs1, socs2, and cis genes were not transcribed. In
      transfection assays, SOCS3 was found to suppress the transcriptional response of 
      macrophages to IFN-gamma. A causal link of decreased IFN-gamma signaling to SOCS3
      induction was also suggested by the LPS-dependent reduction of IFN-gamma-mediated
      Janus kinase 1 (JAK1) activation. Further consistent with inhibitory activity of 
      SOCS3, LPS also inhibited the JAK2-dependent activation of Stat5 by GM-CSF. Our
      results thus link the deactivating effect of chronic LPS exposure on macrophages 
      with its ability to induce SOCS3.
FAU - Stoiber, D
AU  - Stoiber D
AD  - Institute of Microbiology and Genetics, Vienna Biocenter, Vienna, Austria.
FAU - Kovarik, P
AU  - Kovarik P
FAU - Cohney, S
AU  - Cohney S
FAU - Johnston, J A
AU  - Johnston JA
FAU - Steinlein, P
AU  - Steinlein P
FAU - Decker, T
AU  - Decker T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 42HK56048U (Tyrosine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Jak1 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - DNA-Binding Proteins/antagonists & inhibitors/biosynthesis/genetics
MH  - Gene Expression Regulation/immunology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/antagonists &
      inhibitors/pharmacology
MH  - Humans
MH  - Interferon-gamma/*physiology
MH  - Janus Kinase 1
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophages/enzymology/*metabolism
MH  - Mice
MH  - Phosphorylation
MH  - *Protein Biosynthesis
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Proteins/genetics
MH  - *Repressor Proteins
MH  - STAT1 Transcription Factor
MH  - Signal Transduction/*immunology
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins
MH  - Time Factors
MH  - Trans-Activators/antagonists & inhibitors/biosynthesis/genetics
MH  - *Transcription Factors
MH  - Transfection
MH  - Tyrosine/metabolism
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - ji_v163n5p2640 [pii]
PST - ppublish
SO  - J Immunol. 1999 Sep 1;163(5):2640-7.