Ar. Khaled et al., FUNCTIONAL CONSEQUENCES OF THE SHP-1 DEFECT IN MOTH-EATEN VIABLE MICE- ROLE OF NF-KAPPA-B, Cellular immunology, 185(1), 1998, pp. 49-58
To define the functional consequences of the src-homology domain-1 pro
tein (SHP-1) defect, we examined cytokine production and NF-kappa B ac
tivity in motheaten viable (Mev) mice. We found elevated levels of int
erleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF)
, and interferon-gamma (IFN-gamma) in Mev mice sera and cultured B and
T cells compared to littermate control adult mice. The levels of inte
rleukin-a (IL-2) detected in Mev sera and activated Mev T cells were d
ecreased, but IL-2 receptor expression was increased. We then evaluate
d the activity of NF-kappa B and found that this protein is highly exp
ressed in Mev B and T cells. To determine if NF-kappa B had a role in
causing the elevated levels of cytokines in Mev mice, we treated activ
ated Mev T cells with an NF-kappa B decoy and found that cell culture
treatment with the decoy resulted in significant reduction of the secr
etion of IL-6, GM-CSF, and TNF, but not IFN-gamma. Therefore, our data
show that Mev mice secrete elevated levels of inflammatory cytokines,
which can be mediators in the development of the Mev clinical disorde
r, and that NF-kappa B has an important role in this process, impactin
g upon the regulation of the immune response. (C) 1998 Academic Press.