TRANSFECTION OF HUMAN-MELANOMA CELLS WITH TYPE-I INTERLEUKIN-1 (IL-1) RECEPTOR CDNA RENDERED THEM IL-1-RESPONSIVE AND REVEALED THE IMPORTANCE OF ODC ACTIVITY DOWN-REGULATION IN IL-1-INDUCED GROWTH-INHIBITION

被引:4
作者
YANG, D
HAYASHI, H
HIYAMA, Y
TAKII, T
ONOZAKI, K
机构
[1] NAGOYA CITY UNIV, FAC PHARMACEUT SCI, DEPT HYG CHEM, MIZUHO KU, NAGOYA, AICHI 467, JAPAN
[2] DAIICHI PHARMACEUT CO LTD, TOKYO R&D CTR, EDOGAWA KU, TOKYO 134, JAPAN
关键词
A375 MELANOMA CELLS; IL-1; RECEPTOR; IL-6; ODC;
D O I
10.1093/oxfordjournals.jbchem.a124983
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A human type I IL-1 receptor expression plasmid has been constructed and used to transfect human melanoma cells (A375-5), which have been shown to be unresponsive to the antiproliferative effect of IL-1, Five stable transfectant cell lines have been established, of which three are sensitive and the other two resistant to the anti-proliferative effect of IL-1, All the transfectant cell lines, but not progenitor A375-5 cells, expressed functional type I IL-1 receptors and could produce IL-6 in response to IL-1, suggesting that the unresponsiveness of A375-5 melanoma cells is exactly due to an IL-1 receptor deficiency, The three IL-l-sensitive stable transfectant cell lines expressed much more type I IL-1 receptor than the IL-l-sensitive A375-6 cells, thus they are expected to be useful for investigating the signal transduction pathway of IL-1-induced growth inhibition in melanoma cells, The two resistant cell lines produced comparable amounts of IL-6 in response to IL-1, as sensitive cell lines did, indicating that IL-6 induction does not play a major role in IL-l-induced growth inhibition in these melanoma cells, The possibility of an IL-6 receptor and/or IL-6 receptor signaling deficiency was ruled out as the IL-l-sensitive and -resistant transfectants responded similarly to a high dose of exogenous human recombinant IL-6, Examination of the ornithine decarboxylase (ODC) activity of recombinant human IL-1 alpha treated cells showed that all the sensitive but none of the resistant cell lines could down-regulate their ODC activity, These results suggest that IL-l-induced ODC activity down-regulation is an important step in the signal transduction pathway of IL-1-induced growth inhibition of melanoma cells.
引用
收藏
页码:802 / 809
页数:8
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