TY - JOUR
AU1 - Ludwig, Antje
AU2 - Fechner, Mandy
AU3 - Wilck, Nicola
AU4 - Meiners, Silke
AU5 - Grimbo, Nicole
AU6 - Baumann, Gert
AU7 - Stangl, Verena
AU8 - Stangl, Karl
AB - Proteasome inhibitors are considered to have anti-inflammatory therapeutic potential. However, recent reports addressing proteasome inhibition in the vascular system are controversial, ranging from beneficial anti-inflammatory and anti-oxidative effects to potentiation of inflammation and oxidative stress. This study was based on the hypothesis that the divergent effects might be a result of a differential and dose-dependent responsiveness of vascular cells to proteasome inhibitors. We tested whether low doses of proteasome inhibitors would favor anti-inflammatory effects in vascular cells in vitro and in vivo. Human umbilical vein endothelial cells (HUVEC) were preincubated with proteasome inhibitors MG132 and MG262 at concentrations that did not affect cell viability during a 24-h treatment. Upon addition of tumor necrosis factor alpha (TNF-α) the induced expression of adhesion molecules and the adhesion of monocytic THP-1 cells to HUVECs was significantly lowered. However, nuclear translocation of NF-κB was only slightly diminished. Low-dose pretreatment with proteasome inhibitors decreased TNF-α-induced generation of reactive oxygen species in HUVEC. Bortezomib was administered at a dose of 50 µg/kg body weight to Dahl salt-sensitive rats (DSSR) on high-salt diet. This low-dose proteasome inhibition led to decreased hypertension-induced oxidative stress and reduced expression of vascular cell adhesion molecule 1 (VCAM-1) in the aortae.
TI - Potent anti-inflammatory effects of low-dose proteasome inhibition in the vascular system
JF - Journal of Molecular Medicine
DO - 10.1007/s00109-009-0469-9
DA - 2009-04-28
UR - https://www.deepdyve.com/lp/springer-journals/potent-anti-inflammatory-effects-of-low-dose-proteasome-inhibition-in-33w6rkj6kH
SP - 793
EP - 802
VL - 87
IS - 8
DP - DeepDyve
ER -