Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase

2001 ◽  
Vol 280 (2) ◽  
pp. L326-L333 ◽  
Author(s):  
Steven R. Kleeberger ◽  
Sekhar P. M. Reddy ◽  
Liu-Yi Zhang ◽  
Hye-Youn Cho ◽  
Anne E. Jedlicka
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Specific Inhibitor ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Mrna ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

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.

LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process

2004 ◽  
Vol 287 (5) ◽  
pp. G1008-G1016 ◽  
Author(s):  
Marieke G. L. Elferink ◽  
Peter Olinga ◽  
Annelies L. Draaisma ◽  
Marjolijn T. Merema ◽  
Klaas Nico Faber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Rat Liver ◽  
Inducible Nitric Oxide Synthase ◽  
Human Liver ◽  
Mrna Levels ◽  
Liver Slices ◽  
Oxide Synthase ◽  
Human Liver Slices ◽  
Inducible Nitric Oxide

Endotoxin-induced cholestasis in rodents is caused by hepatic downregulation of transporters, including the basolateral Na+-dependent taurocholate transporter (ntcp) and the canalicular bile salt export pump (bsep) and multidrug resistance-associated protein 2 (mrp2). Details about the regulation of the human transporter proteins during this process are lacking. We used precision-cut human and rat liver slices to study the regulation of transporter expression during LPS-induced cholestasis. We investigated the effect of LPS on nitrate/nitrite and cytokine production in relation to the expression of inducible nitric oxide synthase, NTCP, BSEP, and MRP2 both at the level of mRNA with RT-PCR and protein using immunofluorescence microscopy. In liver slices from both species, LPS-induced expression of inducible nitric oxide synthase was detected within 1–3 h and remained increased over 24 h. In rat liver slices, this was accompanied by a significant decrease of rat ntcp and mrp2 mRNA levels, whereas bsep levels were not affected. These results are in line with previous in vivo studies and validate our liver slice technique. In LPS-treated human liver slices, NTCP mRNA was downregulated and showed an inverse correlation with the amounts of TNF-α and Il-1β produced. In contrast, MRP2 and BSEP mRNA levels were not affected under these conditions. However, after 24-h LPS challenge, both proteins were virtually absent in human liver slices, whereas marker proteins remained detectable. In conclusion, we show that posttranscriptional mechanisms play a more prominent role in LPS-induced regulation of human MRP2 and BSEP compared with the rat transporter proteins.

scholarly journals Plaunol A from Croton stellatopilosus Inhibits Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Macrophage RAW264.7 Cells

2018 ◽  
Vol 13 (7) ◽  
pp. 1934578X1801300
Author(s):  
Charoenwong Premprasert ◽  
Supinya Tewtrakul ◽  
Juraithip Wungsintaweekul
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Cyclooxygenase 2 ◽  
Raw264.7 Cells ◽  
Mrna Levels ◽  
Chromatographic Techniques ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

A clerodane diterpene (plaunol A) and three flavonoids (vitexin; luteolin-7-O-β-D-glucoside and luteolin-4'-O-glucoside) were isolated from stems and leaves of Croton stellatoliosus Ohba, using series of chromatographic techniques. Evaluation for anti-inflammatory activity in LPS-induced RAW264.7 cells revealed that, only plaunol A exhibited the inhibitory activity on nitric oxide production with the IC50 of 11.69 μM. This was no cytotoxic effect to the cells at a concentration of 100 μM, by MTT assay. Determination of mRNA levels by qRT-PCR, indicated that plaunol A suppressed the expressions of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-induced RAW264.7 cells.

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