Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines.
The role of IL-6 in the antiproliferative effect of IL-1 for tumor cell lines was investigated using IL-1-sensitive cell lines. Human recombinant IL-1 alpha and IL-6 both inhibited the growth of an IL-1-sensitive cloned human melanoma cell line (A375-C6). However, IL-1 has greater maximum growth inhibitory activity than IL-6. Conditioned medium of the tumor cells that were treated with IL-1 contained IL-6 as determined by ELISA. Northern blot analysis revealed that IL-6 mRNA expression increased in IL-1-treated cells. In addition, antibody against human IL-6 neutralized about 50% of the antiproliferative effect of IL-1. The growth of an IL-1-resistant clone of A375 cells (A375-C5), which cannot be shown to express any detectable IL-1R, was inhibited by IL-6 to the same degree as A375-C6 cells. The A375-C5 cell line did not produce IL-6 or increase IL-6 mRNA after stimulation with IL-1. These results indicate that IL-6 mediates in part the antiproliferative effect of IL-1 on A375-C6 cells by acting as an autocrine antiproliferative factor. IL-1 also inhibited the growth of a malignant human mammary cell line (MDA-MB-415). IL-6 exhibited only slight growth inhibition in this cell line. Neither IL-6 production nor IL-6 mRNA expression was induced in this cell line by IL-1. Antibody against IL-6 did not neutralize the antiproliferative effect of IL-1. Therefore, for MDA-MB-415 cells IL-6 appeared not to be involved in the antiproliferative effect of IL-1. These results indicate that the antiproliferative effect of IL-1 involves at least two pathways, one IL-6 dependent and another IL-6 independent. The contribution of IL-6 to the antiproliferative effect of TNF was also examined. IL-6 appeared not to play a role in the antiproliferative effect of TNF in these cell lines.
Morinaga
Y
Y
Department of Microbiology, University of Tsukuba, Ibaraki, Japan.
Suzuki
H
H
Takatsuki
F
F
Akiyama
Y
Y
Taniyama
T
T
Matsushima
K
K
Onozaki
K
K
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D008545:Melanoma / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006131:Growth Inhibitors; D007106:Immune Sera; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha