TY  - EJOU
AU  - Laskov, Reuven 
AU  - Berger, Nir 
AU  - Horwitz, Marshall S. 

TI  - Differential effects of tumor necrosis factor-α and CD40L on NF-κB inhibitory proteins IκBα, β and Ɛ and on the induction of the Jun amino-terminal kinase pathway in Ramos Burkitt lymphoma cells
T2  - European Cytokine Network

PY  - 2005
VL  - 16
IS  - 4
SN  - 1952-4005

AB  - Interaction between the CD40 ligand and its cognate receptor is known to affect various aspects of
B-cell biology. Less is known about the biological consequences of B-cell signaling through tumor necrosis factor
alpha (TNF-α) and its two receptors. We have used Ramos germinal center (GC)-derived Burkitt’s lymphoma
(BL) cells as a model system to compare some of the early signaling events of TNF-α and CD40L on the NF-jB
and c-Jun amino-terminal kinase (JNK) pathways. We have previously found that both TNF-α and CD40L
induced enhanced cell aggregation, adherence and modified cell surface morphology of Ramos cells. In the present
report, it was found that treatment with either TNF-α or CD40L resulted in a rapid degradation (within 15 min)
of IκBα, followed by a recovery period lasting up to a few hours. The level of IκBβ, another inhibitory molecule
of the NF-κB pathway, also decreased following treatment with CD40L or TNF-α. However, whereas CD40L
induced a rapid drop without significant recovery within 2 h, TNF-α caused a slow and gradual decline of IκBβ.
In addition, treatment with CD40L resulted in a gradual and modest decline of up to 60% of the level of IκBƐ
within 2 h, whereas a much smaller decline was seen with TNF-α (approx. 20%) Our results thus show that in
Ramos cells, TNF-α and CD40L have common, as well as differential, signaling effects on the IκBα, IκBβ and IjBƐ,
which form inhibitory complex(es) with the NF-κB cytosolic proteins. We also found that CD40L, but not TNF-α
activates the JNK pathway through transient phosphorylation of its threonine183/tyrosine185 residues. As
expected, c-Jun, which is known to be a substrate of JNK, was also phosphorylated at serine residue 73 by
treatment with CD40L, but not by TNF-α.
KW  - TNF-α
KW  -  CD40L
KW  -  IkB proteins
KW  -  JNK
KW  -  signal transduction
KW  -  B lymphoma

DO  -