W. Su et al., The direct effect of IL-12 on tumor cells: IL-12 acts directly on tumor cells to activate NF-kappa B and enhance IFN-gamma-mediated STAT1 phosphorylation, BIOC BIOP R, 280(2), 2001, pp. 503-512
Biochemistry & Biophysics
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
IL-12 directly acts on T cells and NK cells to induce IFN-gamma production.
IFN-gamma plays an important role in anti-tumor effect of IL-12. In spite
of various functions of IL-12 on immunocytes, the direct effect of IL-12 on
tumor cells has not been fully clarified. The present study investigated t
he direct effect of IL-12 on eight murine tumor cell lines in vitro. IL-12
did not directly up-regulate expression of MHC class I on tumor cells, but
enhanced IFN-gamma -induced up-regulation of R-IC class I expression in MC-
38, MCA102, MCA205 and MCA207 cells. IL-12 alone did not activate STAT1, bu
t IL-12 enhanced IFN-gamma -mediated STAT1 phosphorylation in MC-38, MCA102
, MCA205, MCA207 and Colon26-NL-17 cells, which expressed IL-12 receptor be
ta1 mRNA, In the other side, Panc-02, B16-BL6 and 266-6 cells were not affe
cted by IL-12, in which expression of IL-12 receptor beta1 mRNA was not det
ected. Anti-IL-12 mAb inhibited the direct effect of IL-12 on MC-38 cells.
Moreover, nuclear localization of NF-kappaB was observed after stimulation
of IL-12 or IL-12 p40 in MC-38 and Colon-26-NL-17 cells, but not in Panc-02
cells. These findings suggest that IL-12 directly acts on tumor cells thro
ugh IL-12 receptor beta1 to activate NF-kappaB and enhance IFN-gamma -media
ted STAT1 phosphorylation. (C) 2001 Academic Press.