NF‐κB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF‐α cytotoxicity in L929 cells

Abstract

Tumor necrosis factor alpha (TNF-a) is one of the best-described cell death promoters. In murine L929 fibroblasts, dexamethasone inhibits TNF-a-induced cytotoxicity. Since phosphatidyl inositol 3 kinase (PI3K) and nuclear factor kappa B (NF-jB) proteins regulate several survival pathways, we evaluated their participation in dexamethasone protection against TNF-a cell death. We interfered with these pathways by overexpressing a negative dominant mutant of PI3K or a non-degradable mutant of inhibitor of NF-jB alpha (IjBa) (the cytoplasmic inhibitor of NF-jB) in L929 cells. The mutant IjB, but not the mutant PI3K, abrogated dexamethasone-mediated protection. The loss of dexamethasone protection was associated with a diminished accumulation in XIAP and c-IAP proteins.

Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils

“…Similarly, XIAP has been shown to be stabilized by glucocorticoids in 2 different cancer cell lines. 6,7 Enhanced levels of XIAP in glucocorticoid-treated neutrophils might partially account for the decreased activity of caspase-3 observed at all time points in neutrophil cultures.…”

Glycosylated VCAM-1 isoforms revealed in 2D western blots of HUVECs treated with tumoral soluble factors of breast cancer cells

“…As a control, actin was simultaneously detected, using a mouse anti-human actin antibody. The antibody was diluted 1:1000 and developed using the same secondary antibody and chemiluminescence system previously described [54]. …”

The Molecular Mechanisms of Glucocorticoids-Mediated Neutrophil Survival

“…However, although glucocorticoids are most notorious for their apoptosis inducing properties, it has become increasingly clear that they can also inhibit apoptosis and induce survival in many cell types [55-70]. Various mechanisms for glucocorticoid mediated inhibition of apoptosis have been proposed that include up-regulation of anti-apoptotic Bcl-2 family members [55, 56, 70]; stabilization [62] and induction [68] of IAPs; activation of NF-κB [59, 61]; suppression of components of the extrinsic pathway of apoptosis [57, 65]; and induction of signaling molecules such as MAPK phosphatase-1 (MKP-1) and Serum and glucocorticoid activated kinase-1 (SGK-1) [63, 69] (Table 1 ).…”