Interleukin-6 stimulates cell proliferation of rat pituitary clonal cell lines in vitro
- 6 Downloads
We investigated the effect of recombinant human IL-6 (rhlL-6) on cell proliferation using the MtT/E rat pituitary tumor cell line, which was recently established by Inoue et al. This cell line expresses the homeodomain protein Pit-1/GHF 1 and does not produce any significant amount of pituitary hormones, but retains its tumorigenicity by back-transplantation into rats, resulting in production of prolactin. MtT/E cells were seeded into Falcon 24-well plates at a density of 2×104 cells/well in a cultured medium, containing 10% horse serum and 2.5% fetal bovine, with test drug. After four-days (12 days for the time-course study) incubations, the cells were counted using a hemocytometer. Incubation for 4 days with rhlL-6 caused concentration-dependent stimulation of MtT/E cell growth and [3H]-thymidine incorporation into MtT/E cells. Addition of 20 ng/ml rhlL-6 to the culture medium stimulated MtT/E cell growth in a time-dependent manner, withdrawal of rhlL-6 from the culture medium reduced MtT/E cell growth, and re-addition of rhlL-6 to the culture medium again stimulated MtT/E cell growth. Among the cytokines tested, granulocyte colony-stimulating factor (rh G-CSF) also showed a slight but significant mitogenic activity on the MtT/E cells. Analysis of 125|-rhlL-6 binding to the MtT/E cells indicated a dissociation constant of 0.953×10−9 mmol/l and the presence of 968 binding sites per cell. These results confirm the previous finding that IL-6 exerts mitogenic activity on pituitary tumor cells and also support the hypothsis that IL-6 may be involved in the control of cell growth and proliferation in the pituitary.
Key-wordsInterleukin-6 interleukin-1 pituitary tumor cell cell growth lnterleukin-6 binding site
Unable to display preview. Download preview PDF.
- 6.Yamaguchi M., Matsuzaki N., Hirota K., Miyake A., Tanizawa O. lnterleukin-6 possibly induced by interleukin-1ß in the pituitary gland stimulates the releases of gonadotropins and prolactin. Acta Endocrinol. (Copenh.) 122: 201, 1990.Google Scholar
- 8.Jones T.H., Daniels M., James R.A., Justice S.K., McCorkle R., Price A., Kendall-Taylor P., Weetman A.P. Production of bioactive and immunoreactive inter-leukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas. J. Clin. Endocrinol. Metab. 78: 180, 1994.PubMedGoogle Scholar
- 11.Tatsuno I., Somogyvari-vigh A., Mizuno K., Gottschall P.E., Hidaka H., Arimura A. Neuropeptide regulation of interleukin-6 production from the pituitary: Stimulation by pituitary adenylate cyclase activating polypeptide and calcitonin generelated peptide. Endocrinology 129: 1797, 1991.PubMedCrossRefGoogle Scholar
- 44.Fukunaga R., Ikeda E., Pan C., Seto Y., Nagata S. Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J. 70: 2855, 1991.Google Scholar