Role of IL-6 and CD23 in the resistance to growth arrest and apoptosis in LCL41 B lymphoma cells.
Interleukin-6 (IL-6) is a growth and survival factor in Epstein-Barr virus (EBV)-infected B lymphoma cells and IL-6 antagonists have been used in clinical practice for this pathology. We thus wanted to investigate the effect of the IL-6 receptor antagonist Sant7 on proliferative and anti-apoptotic signals in the IL-6-secreting LCL41 B lymphoid cells, taken from a patient with EBV-induced lymphoproliferative disorder. Results show efficient inhibition of constitutive Stat3 activation by Sant7. However, this inhibition is associated with marginal induction of apoptosis and with minor decrease of cell proliferation, contrary to the effect of the Jak kinase inhibitor AG490, which down-regulates both proliferation and Stat3 activation. Anti-apoptotic markers such as Bcl-xL or Mcl-1 are constitutively expressed in these cells, and their expression is not affected by Sant7 treatment. Inhibition of Stat3 activation is therefore not sufficient to prevent proliferation and to induce apoptosis in these cells. In addition, low cell density is a condition favouring inhibition of cell clustering and anti-proliferative Sant7 activity. A marked inhibition of cell cluster formation and proliferation is achieved by antibody treatment against the CD23 mature B cell surface marker expressed in LCL41 cells. These findings may thus contribute to the identification of possible resistance mechanisms to growth arrest in B cell lymphoproliferative conditions.
Militi
Stefania
S
Department of Immunology, Sigma-Tau SpA R&D, Via Pontina Km 30400, Pomezia, 00040 Rome, Italy.
Chiapparino
Caterina
C
Testa
Ugo
U
Carminati
Paolo
P
De Santis
Rita
R
Serlupi-Crescenzi
Ottaviano
O
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D016393:Lymphoma, B-Cell / Q000473:pathology*; D017455:Receptors, IgE / Q000502:physiology*
D015850:Interleukin-6; D017455:Receptors, IgE