Abstract
We previously demonstrated that colony stimulating factor (CSF)-producing cell lines co-produce interleukin-1 (IL-1) and IL-6 in addition to CSFs. In the present study, we examined the role of IL-1 production in three human tumour cell lines producing granulocyte (G)-CSF, IL-1 and IL-6. Addition of anti-human IL-1 alpha antiserum to the culture caused a 90-62% reduction of G-CSF and a 85-44% reduction of IL-6 production, respectively, as evaluated by enzyme immunoassay in all three cell lines. The decrease of G-CSF and IL-6 production by the anti-IL-1 alpha antiserum was also confirmed at the level of mRNA expression. The anti-IL-1 alpha antiserum did not affect the growth of these cell lines. Excess recombinant IL-1 alpha exogenously added to the culture enhanced G-CSF and IL-6 production in all three cell lines. However, IL-1 alpha had little effect on the growth of these three cell lines. Neither anti-IL-6 nor anti-G-CSF antibodies affected the production of the other cytokines. These results indicate that IL-1 alpha regulates G-CSF and IL-6 production in these tumour cell lines, and suggest that the IL-1 production plays an important role in CSF-producing tumours.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990 Jun;9(6):1897–1906. doi: 10.1002/j.1460-2075.1990.tb08316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Demetri G. D., Zenzie B. W., Rheinwald J. G., Griffin J. D. Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro. Blood. 1989 Aug 15;74(3):940–946. [PubMed] [Google Scholar]
- Fibbe W. E., Daha M. R., Hiemstra P. S., Duinkerken N., Lurvink E., Ralph P., Altrock B. W., Kaushansky K., Willemze R., Falkenburg J. H. Interleukin 1 and poly(rI).poly(rC) induce production of granulocyte CSF, macrophage CSF, and granulocyte-macrophage CSF by human endothelial cells. Exp Hematol. 1989 Mar;17(3):229–234. [PubMed] [Google Scholar]
- Fibbe W. E., van Damme J., Billiau A., Voogt P. J., Duinkerken N., Kluck P. M., Falkenburg J. H. Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes. Blood. 1986 Dec;68(6):1316–1321. [PubMed] [Google Scholar]
- Matsuda T., Hirano T., Kishimoto T. Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL 6 monoclonal antibodies. Eur J Immunol. 1988 Jun;18(6):951–956. doi: 10.1002/eji.1830180618. [DOI] [PubMed] [Google Scholar]
- Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
- Nishizawa M., Tsuchiya M., Watanabe-Fukunaga R., Nagata S. Multiple elements in the promoter of granulocyte colony-stimulating factor gene regulate its constitutive expression in human carcinoma cells. J Biol Chem. 1990 Apr 5;265(10):5897–5902. [PubMed] [Google Scholar]
- Okuno Y., Takahashi T., Suzuki A., Fukumoto M., Nakamura K., Imura H. Co-production of interleukin-1 and interleukin-6 in tumor cell lines elaborating colony-stimulating factors. Jpn J Cancer Res. 1991 Aug;82(8):890–892. doi: 10.1111/j.1349-7006.1991.tb01917.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato K., Fujii Y., Kakiuchi T., Kasono K., Imamura H., Kondo Y., Mano H., Okabe T., Asano S., Takaku F. Paraneoplastic syndrome of hypercalcemia and leukocytosis caused by squamous carcinoma cells (T3M-1) producing parathyroid hormone-related protein, interleukin 1 alpha, and granulocyte colony-stimulating factor. Cancer Res. 1989 Sep 1;49(17):4740–4746. [PubMed] [Google Scholar]
- Schaafsma M. R., Fibbe W. E., Van Damme J., Duinkerken N., Ralph P., Kaushansky K., Altrock B. W., Willemze R., Falkenburg J. H. Interleukin-6 is not involved in the interleukin-1-induced production of colony-stimulating factors by human bone marrow stromal cells and fibroblasts. Blood. 1989 Dec;74(8):2619–2623. [PubMed] [Google Scholar]
- Seelentag W., Mermod J. J., Vassalli P. Interleukin 1 and tumor necrosis factor-alpha additively increase the levels of granulocyte-macrophage and granulocyte colony-stimulating factor (CSF) mRNA in human fibroblasts. Eur J Immunol. 1989 Jan;19(1):209–212. doi: 10.1002/eji.1830190135. [DOI] [PubMed] [Google Scholar]
- Slack J. L., Nemunaitis J., Andrews D. F., 3rd, Singer J. W. Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40. Blood. 1990 Jun 15;75(12):2319–2327. [PubMed] [Google Scholar]
- Suzuki A., Takahashi T., Okuno Y., Nakamura K., Tashiro H., Fukumoto M., Konaka Y., Imura H. Analysis of abnormal expression of g-csf gene in a novel tumor cell line (KHC 287) elaborating G-CSF, IL-1 and IL-6 with co-amplification of c-myc and c-ki-ras. Int J Cancer. 1991 May 30;48(3):428–433. doi: 10.1002/ijc.2910480321. [DOI] [PubMed] [Google Scholar]
- Watari K., Asano S., Shirafuji N., Kodo H., Ozawa K., Takaku F., Kamachi S. Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay. Blood. 1989 Jan;73(1):117–122. [PubMed] [Google Scholar]