Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase
Copyright policy )Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase
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 O3exposure. Pretreatment of O3-susceptible C57BL/6J mice with a specific inhibitor of total NOS ( NG-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 O3relative 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.
- Johns Hopkins University United States
Male, Mice, Knockout, Membrane Glycoproteins, Neutrophils, Nitric Oxide Synthase Type II, Cell Count, Epithelial Cells, Mice, Inbred Strains, Capillary Permeability, Mice, Ozone, Administration, Inhalation, Macrophages, Alveolar, Animals, Drosophila Proteins, Enzyme Inhibitors, Nitric Oxide Synthase, Bronchoalveolar Lavage Fluid, Lung, Injections, Intraperitoneal
Male, Mice, Knockout, Membrane Glycoproteins, Neutrophils, Nitric Oxide Synthase Type II, Cell Count, Epithelial Cells, Mice, Inbred Strains, Capillary Permeability, Mice, Ozone, Administration, Inhalation, Macrophages, Alveolar, Animals, Drosophila Proteins, Enzyme Inhibitors, Nitric Oxide Synthase, Bronchoalveolar Lavage Fluid, Lung, Injections, Intraperitoneal
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).92 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!