PMID- 16766576
OWN - NLM
STAT- MEDLINE
DCOM- 20061107
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 291
IP  - 4
DP  - 2006 Oct
TI  - The transcriptional response to lipopolysaccharide reveals a role for 
      interferon-gamma in lung neutrophil recruitment.
PG  - L677-82
AB  - Neutrophil recruitment to the lung after lipopolysaccharide (LPS; endotoxin) 
      inhalation is primarily dependent on Toll-like receptor 4 (Tlr4) signaling, 
      because it is virtually absent in mice deficient in Tlr4. However, among strains 
      wild type for Tlr4, the magnitude of neutrophil recruitment to the lung after LPS 
      inhalation is variable, suggesting the involvement of genes other than Tlr4. To 
      identify genes associated with the inflammatory response to inhaled LPS, we 
      evaluated the transcriptional response in lungs of 12 inbred strains of mice, 8 
      which are wild type for Tlr4 and 4 of which lack functional Tlr4. Using the 
      promoter integration in microarray analysis algorithm, we scanned our gene list 
      for transcription factor-binding sites significantly overrepresented among Tlr4 
      wild-type strains with high neutrophil influx in the lung after LPS inhalation. 
      This analysis identified the interferon (IFN)-stimulated response element (ISRE) 
      as the most overrepresented transcription factor (present in 24% of the 
      promoters) associated with the neutrophil influx to the lower respiratory tract. 
      To test the validity of this observation, we evaluated IFN-gamma-deficient mice 
      and found that the presence of IFN-gamma is essential for robust neutrophil 
      recruitment to the lower respiratory tract and modulation of key regulatory 
      cytokines and chemokines after LPS inhalation. In conclusion, using a genomic 
      approach, we identified the ISRE as a transcriptional element associated with the 
      neutrophil response to inhaled LPS and demonstrated for the first time that 
      IFN-gamma plays a critical role in LPS-induced neutrophil recruitment to the 
      lower airways.
FAU - Burch, Lauranell H
AU  - Burch LH
AD  - National Institute of Environmental Health Sciences, Division of Pulmonary, 
      Allergy, and Critical Care Medicine, Research Triangle Park, NC 27709, USA. 
      burchl@niehs.nih.gov
FAU - Yang, Ivana V
AU  - Yang IV
FAU - Whitehead, Gregory S
AU  - Whitehead GS
FAU - Chao, Frank G
AU  - Chao FG
FAU - Berman, Katherine G
AU  - Berman KG
FAU - Schwartz, David A
AU  - Schwartz DA
LA  - eng
GR  - ES-011961/ES/NIEHS NIH HHS/United States
GR  - ES-012496/ES/NIEHS NIH HHS/United States
GR  - ES-07498/ES/NIEHS NIH HHS/United States
GR  - ES-11375/ES/NIEHS 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.
DEP - 20060609
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factors)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Gene Expression/drug effects
MH  - Interferon-gamma/*physiology
MH  - Interferons/physiology
MH  - Lipopolysaccharides/administration & dosage/*pharmacology
MH  - Lung/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Neutrophil Infiltration/genetics/*physiology
MH  - Pneumonia/chemically induced/genetics
MH  - Response Elements/physiology
MH  - Toll-Like Receptor 4/deficiency/physiology
MH  - Transcription Factors/physiology
MH  - Transcription, Genetic/*drug effects
EDAT- 2006/06/13 09:00
MHDA- 2006/11/09 09:00
CRDT- 2006/06/13 09:00
PHST- 2006/06/13 09:00 [pubmed]
PHST- 2006/11/09 09:00 [medline]
PHST- 2006/06/13 09:00 [entrez]
AID - 00523.2005 [pii]
AID - 10.1152/ajplung.00523.2005 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L677-82. doi: 
      10.1152/ajplung.00523.2005. Epub 2006 Jun 9.