PMID- 11159012
OWN - NLM
STAT- MEDLINE
DCOM- 20010308
LR  - 20220223
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 280
IP  - 2
DP  - 2001 Feb
TI  - Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via 
      inducible nitric oxide synthase.
PG  - L326-33
AB  - We tested the hypotheses that 1) inducible nitric oxide synthase (iNOS) mediates 
      ozone (O3)-induced lung hyperpermeability and 2) mRNA levels of the gene for iNOS 
      (Nos2) are modulated by Toll-like receptor 4 (Tlr4) during O3 exposure. 
      Pretreatment of O3-susceptible C57BL/6J mice with a specific inhibitor of total 
      NOS (N(G)-monomethyl-L-arginine) significantly decreased the mean lavageable 
      protein concentration (a marker of lung permeability) induced by O3 (0.3 
      parts/million for 72 h) compared with vehicle control mice. Furthermore, 
      lavageable protein in C57BL/B6 mice with targeted disruption of Nos2 [Nos2(-/-)] 
      was 50% less than the protein in wild-type [Nos2(+/+)] mice after O3. To 
      determine whether Tlr4 modulates Nos2 mRNA levels, we studied C3H/HeJ (HeJ) and 
      C3H/HeOuJ mice that differ only at a missense mutation in Tlr4 that confers 
      resistance to O3-induced lung hyperpermeability in the HeJ strain. Nos2 and Tlr4 
      mRNA levels were significantly reduced and correlated in resistant HeJ mice after 
      O3 relative to those in susceptible C3H/HeOuJ mice. Together, the results are 
      consistent with an important role for iNOS in O3-induced lung hyperpermeability 
      and suggest that Nos2 mRNA levels are mediated through Tlr4.
FAU - Kleeberger, S R
AU  - Kleeberger SR
AD  - Department of Environmental Health Sciences, The Johns Hopkins University School 
      of Public Health, Baltimore, Maryland 21205, USA. skleeber@jhsph.edu
FAU - Reddy, S P
AU  - Reddy SP
FAU - Zhang, L Y
AU  - Zhang LY
FAU - Cho, H Y
AU  - Cho HY
FAU - Jedlicka, A E
AU  - Jedlicka AE
LA  - eng
GR  - ES-03819/ES/NIEHS NIH HHS/United States
GR  - ES-09606/ES/NIEHS NIH HHS/United States
GR  - R01-HL-57142/HL/NHLBI NIH HHS/United States
GR  - R29-HL-58122/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
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 (Drosophila Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 66H7ZZK23N (Ozone)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/chemistry/cytology
MH  - Capillary Permeability/*drug effects
MH  - Cell Count
MH  - *Drosophila Proteins
MH  - Enzyme Inhibitors/administration & dosage
MH  - Epithelial Cells/cytology
MH  - Injections, Intraperitoneal
MH  - Lung/blood supply/drug effects/*metabolism
MH  - Macrophages, Alveolar/cytology
MH  - Male
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Neutrophils/cytology
MH  - Nitric Oxide Synthase/antagonists & inhibitors/genetics/*metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Ozone/administration & dosage/*toxicity
MH  - Proteins/analysis
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - omega-N-Methylarginine/administration & dosage
EDAT- 2001/02/13 11:00
MHDA- 2001/03/10 10:01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/03/10 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
AID - 10.1152/ajplung.2001.280.2.L326 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2001 Feb;280(2):L326-33. doi: 
      10.1152/ajplung.2001.280.2.L326.