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

Citation
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
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
280
Issue
2
Year of publication
2001
Pages
503 - 512
Database
ISI
SICI code
0006-291X(20010119)280:2<503:TDEOIO>2.0.ZU;2-2
Abstract
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.