PMID- 16940747
OWN - NLM
STAT- MEDLINE
DCOM- 20061213
LR  - 20231213
IS  - 1018-2438 (Print)
IS  - 1018-2438 (Linking)
VI  - 141
IP  - 4
DP  - 2006
TI  - Murine TLR4 is implicated in cigarette smoke-induced pulmonary inflammation.
PG  - 354-68
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an 
      abnormal inflammatory response of the lungs to noxious particles or gases. We 
      investigated whether Toll-like receptor 4 (TLR4) is implicated in cigarette smoke 
      (CS)-induced pulmonary inflammation in a murine model of COPD. METHODS: C3H/HeOuJ 
      (Tlr4(WT)) and C3H/HeJ (Tlr4(defective)) mice were exposed to air or CS for 5 
      weeks (subacute) and 26 weeks (chronic), and pulmonary inflammation was 
      evaluated. RESULTS: In Tlr4(WT) mice, subacute and chronic CS exposure induced a 
      substantial pulmonary infiltration of macrophages, neutrophils, lymphocytes and 
      dendritic cells (DCs), that was absent in air-exposed mice. CS exposure increased 
      the costimulatory marker expression on DCs, the levels of monocyte 
      chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in 
      bronchoalveolar lavage (BAL) fluid and induced the pulmonary expression of matrix 
      metalloproteinase-12 (MMP-12), TLR4 and TLR2. In contrast, after subacute CS 
      exposure, Tlr4(defective) mice showed a limited (5-fold lower) increase of DCs 
      and lymphocytes in BAL fluid, lower costimulatory marker expression on DCs and 
      lower MCP-1 and TNF-alpha levels in BAL fluid compared to Tlr4(WT) animals. After 
      chronic CS exposure, however, the difference in pulmonary inflammation between 
      Tlr4(WT) and Tlr4(defective) mice was less pronounced and both strains showed 
      similar MCP-1 and TNF-alpha levels in BAL and similar pulmonary MMP-12, TLR4 and 
      TLR2 expression. CONCLUSIONS: We demonstrated that the TLR4 mutation in C3H/HeJ 
      mice is protective against CS-induced pulmonary influx of neutrophils, DCs and 
      lymphocytes upon subacute CS exposure. However, TLR4 is only of minor importance 
      in chronic CS-induced inflammation in mice.
FAU - Maes, Tania
AU  - Maes T
AD  - Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium. 
      tania.maes@Ugent.be
FAU - Bracke, Ken R
AU  - Bracke KR
FAU - Vermaelen, Karim Y
AU  - Vermaelen KY
FAU - Demedts, Ingel K
AU  - Demedts IK
FAU - Joos, Guy F
AU  - Joos GF
FAU - Pauwels, Romain A
AU  - Pauwels RA
FAU - Brusselle, Guy G
AU  - Brusselle GG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060829
PL  - Switzerland
TA  - Int Arch Allergy Immunol
JT  - International archives of allergy and immunology
JID - 9211652
RN  - 0 (CD11c Antigen)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Smoke)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.65 (Matrix Metalloproteinase 12)
SB  - IM
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - CD11c Antigen/analysis
MH  - Chemokine CCL2/biosynthesis
MH  - Dendritic Cells/physiology
MH  - Inflammation/*etiology
MH  - Lung/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 12/biosynthesis
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Pulmonary Disease, Chronic Obstructive/*etiology
MH  - Smoke/*adverse effects
MH  - Nicotiana/*adverse effects
MH  - Toll-Like Receptor 2/biosynthesis
MH  - Toll-Like Receptor 4/*physiology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2006/08/31 09:00
MHDA- 2006/12/14 09:00
CRDT- 2006/08/31 09:00
PHST- 2005/09/07 00:00 [received]
PHST- 2006/04/20 00:00 [accepted]
PHST- 2006/08/31 09:00 [pubmed]
PHST- 2006/12/14 09:00 [medline]
PHST- 2006/08/31 09:00 [entrez]
AID - 95462 [pii]
AID - 10.1159/000095462 [doi]
PST - ppublish
SO  - Int Arch Allergy Immunol. 2006;141(4):354-68. doi: 10.1159/000095462. Epub 2006 
      Aug 29.