| First Author | Kleeberger SR | Year | 2001 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 280 |
| Issue | 2 | Pages | L326-33 |
| PubMed ID | 11159012 | Mgi Jnum | J:108671 |
| Mgi Id | MGI:3624493 | Doi | 10.1152/ajplung.2001.280.2.L326 |
| Citation | Kleeberger SR, et al. (2001) Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase. Am J Physiol Lung Cell Mol Physiol 280(2):L326-33 |
| abstractText | 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. |
