PMID- 16983331
OWN - NLM
STAT- MEDLINE
DCOM- 20061219
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 86
IP  - 11
DP  - 2006 Nov
TI  - Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin, 
      independent of TRIF, IL-1 and IL-18 pathways.
PG  - 1126-35
AB  - Inhaled endotoxins induce an acute inflammatory response in the airways mediated 
      through Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 
      (MyD88). However, the relative roles of the TLR4 adaptor proteins TIRAP and TRIF 
      and of the MyD88-dependent IL-1 and IL-18 receptor pathways in this response are 
      unclear. Here, we demonstrate that endotoxin-induced acute bronchoconstriction, 
      vascular damage resulting in protein leak, Th1 cytokine and chemokine secretion 
      and neutrophil recruitment in the airways are abrogated in mice deficient for 
      either TIRAP or MyD88, but not in TRIF deficient mice. The contribution of other 
      TLR-independent, MyD88-dependent signaling pathways was investigated in IL-1R1, 
      IL-18R and caspase-1 (ICE)-deficient mice, which displayed normal airway 
      responses to endotoxin. In conclusion, the TLR4-mediated, bronchoconstriction and 
      acute inflammatory lung pathology to inhaled endotoxin critically depend on the 
      expression of both adaptor proteins, TIRAP and MyD88, suggesting cooperative 
      roles, while TRIF, IL-1R1, IL-18R signaling pathways are dispensable.
FAU - Togbe, Dieudonnee
AU  - Togbe D
AD  - Molecular Immunology and Embryology, CNRS UMR6218, Transgenose Institute, 
      Orleans, France.
FAU - Aurore, Gorse
AU  - Aurore G
FAU - Noulin, Nicolas
AU  - Noulin N
FAU - Quesniaux, Valerie F J
AU  - Quesniaux VF
FAU - Schnyder-Candrian, Silvia
AU  - Schnyder-Candrian S
FAU - Schnyder, Bruno
AU  - Schnyder B
FAU - Vasseur, Virginie
AU  - Vasseur V
FAU - Akira, Shizuo
AU  - Akira S
FAU - Hoebe, Kasper
AU  - Hoebe K
FAU - Beutler, Bruce
AU  - Beutler B
FAU - Ryffel, Bernhard
AU  - Ryffel B
FAU - Couillin, Isabelle
AU  - Couillin I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060918
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Endotoxins)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-18)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (TIRAP protein, mouse)
RN  - 67924-63-4 (endotoxin, Escherichia coli)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/metabolism
MH  - Animals
MH  - Bronchi/*drug effects/metabolism/pathology
MH  - Bronchoalveolar Lavage Fluid
MH  - Bronchoconstriction/*drug effects
MH  - Cells, Cultured
MH  - Endotoxins/*toxicity
MH  - Interleukin-1/metabolism
MH  - Interleukin-18/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Lung/drug effects/metabolism/pathology
MH  - Macrophages/drug effects/metabolism
MH  - Membrane Glycoproteins/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/*physiology
MH  - Peroxidase/metabolism
MH  - Receptors, Interleukin-1/*physiology
EDAT- 2006/09/20 09:00
MHDA- 2006/12/21 09:00
CRDT- 2006/09/20 09:00
PHST- 2006/09/20 09:00 [pubmed]
PHST- 2006/12/21 09:00 [medline]
PHST- 2006/09/20 09:00 [entrez]
AID - S0023-6837(22)01765-2 [pii]
AID - 10.1038/labinvest.3700473 [doi]
PST - ppublish
SO  - Lab Invest. 2006 Nov;86(11):1126-35. doi: 10.1038/labinvest.3700473. Epub 2006 
      Sep 18.