Infection of B cells with Epstein-Barr Virus (EBV) induces
interleukin-10 (IL-10) production, which may contribute to transformation.
IL-10 can modulate the immune response at certain levels, playing a crucial role in balancing humoral and cellular responses. Moreover, it can function as a growth and differentiation factor for B cells. However, the mechanism of
IL-10 induction is still unclear. Here we demonstrate that
IL-10 was specifically induced by the EBV-latent
membrane protein 1 (LMP1) in
Burkitt's lymphoma (BL) cell lines BL2 and BL41. In two T cell lines (Jurkat, MOLT3), two NHL cell lines (U266, MHH-PREB1), or three
Hodgkin's disease (HD) cell lines (L428, L540, and KMH2), LMP1 did not induce
IL-10 expression. In contrast, LMP1 activated CD40 or CD54 (ICAM1) expression in the analyzed cell lines. LMP1 derivatives lacking the C-terminal activation regions (CTAR), by deletion of the
amino acids between 187 and 351 (Delta CTAR1) or 232 and 386 (Delta CTAR2), alone, or together induced
IL-10 at very low amounts compared to wild-type LMP1. Inhibition of LMP1-mediated
NF kappa B activation by constitutive repressive
I kappa B-alpha only marginally impaired
IL-10 expression in BL2 cells, while SB2035080 at 5 microM (a specific p38/
SAPK2 inhibitor) led to reduced
IL-10 expression. Our findings confirm the role of LMP1 in transactivation of cellular genes possibly important for
tumor immunoescape but show that more than one signaling pathway is involved in this activation and suggests the necessity of a defined conformation of CTARs to activate
IL-10 involving p38/
SAPK2.