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  3. Medizin - Open Access LMU - Teil 15/22 Podcast
  4. A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.
Background and aims: The transcription factor nuclear factor kappa
B (NF-kB) has risen as a promising target for anti-inflammatory
therapeutics. In the liver, however, NFkB inhibition mediates both
damaging and protective effects. The outcome is deemed to depend on
the liver cell type addressed. Recent gene knock-out studies
focused on the role of NF-kB in hepatocytes, whereas the role of
NF-kB in Kupffer cells has not yet been investigated in vivo. Here
we present a novel approach, which may be suitable for clinical
application, to selectively target NF-kB in Kupffer cells and
analyse the effects in experimental models of liver injury.
Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded
upon gelatin nanoparticles (D-NPs) and their in vivo distribution
was determined by confocal microscopy. Liver damage, NF-kB
activity, cytokine levels and apoptotic protein expression were
evaluated after lipopolysaccharide (LPS), D-galactosamine
(GalN)/LPS, or concanavalin A (ConA) challenge and partial warm
ischaemia and subsequent reperfusion, respectively. Results: D-NPs
were selectively taken up by Kupffer cells and inhibited NF-kB
activation. Inhibition of NF-kB in Kupffer cells improved survival
and reduced liver injury after GalN/LPS as well as after ConA
challenge. While anti-apoptotic protein expression in liver tissue
was not reduced, pro-apoptotic players such as cJun N-terminal
kinase (JNK) were inhibited. In contrast, selective inhibition of
NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting
decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel
tool to selectively inhibit NF-kB activation in Kupffer cells in
vivo. Thus, liver injury can be reduced in experimental fulminant
hepatitis, but increased at ischaemia–reperfusion.

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„A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.“

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