Summary
The present study demonstrates interleukin-1 (IL-1) production by human glioblastorna cells bothin vitro andin vivo. The presence of IL-1α and IL-1β transcripts was analyzed in 4 cell lines. IL-1α mRNA was expressed constitutively in one cell line whereas constitutive IL-1β mRNA could not be detected in any of the cell lines. IL-1α transcripts could be induced with phorbol myristate acetate (PMA) or PMA plus lipopolysaccharide (LPS) in 2 of 4 cell Unes and IL-1β mRNA in 2 of 4 cell lines. Culture fluid from these cell lines was tested for the presence of IL-1 using a specific radioimmuno-assay for either IL-1α or IL-1β. In agreement with the results on RNA, one of 4 cell lines was found to constitutively produce IL-1α but not IL-1β. After treatment with PMA and LPS, IL-1α was detected in the culture fluid from two other lines and IL-1β in the medium from three lines. That the IL-1 produced by these cell lines was biologically active was confirmed in a two step thymocyte proliferation assay. IL-1 like activity was detected in all samples that were positive in the radio-immuno-assay.
Finally, immunohistological analysis on fresh frozen tumour sections provided evidence for IL-1 production by glioblastoma cellsin vivo. Fourteen out of 28 glioblastomas were stained with an anti-IL-1α monoclonal antibody while none of them was stained with an anti-IL-1β antibody.
Similar content being viewed by others
Abbreviations
- GFAP:
-
glial fibrillary acidic protein
- MAb:
-
monoclonal antibody
- IL-1:
-
interleukin-1
- PMA:
-
phorbol myristate acetate
- LPS:
-
lipopolysaccharide
- RIA:
-
radio-immuno-assay
References
Baumann H, Onorato V, Gauldie J, Jahreis GP (1987) Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J Biol Chem 262: 9756–9768
Bodmer S, Strommer K, Frei K, Siepl C, de Tribolet N, Heid I, Fontana A (1989) Immunosuppression and transforming growth factor-β in glioblastoma. J Immunol 143: 3222–3229
Boraschi D, Villa L, Volpini G, Bossu P, Censini S, Ghiara P, Scapigliat G, Nencioni L, Bartalini M, Matteucci G, Cioli F, Carnasciali M, Olmastroni E, Mengozzi M, Ghezzi P, Tagliabue A (1990) Differential activity of interleukin-1α and interleukin-1β in the stimulation of the immune responsein vivo. Eur J Immunol 20: 317–321
Brooks WH, Netsky MG, Normansell DE, Horwitz DA (1972) Depressed cell-mediated immunity in patients with primary intracranial tumours. J Exp Med 136: 1631–1647
Carrel S, Salvi S, Gallay P, Rapin C, Sekaly RP (1991) Positive signal transduction via surface CD 4 molecules does not need co-expression of the CD 3/TcR complex. Res Immunol 142: 97–108
Coceani F, Lees J, Dinarello CA (1988) Occurrence of interleukin-1 in cerebrospinal fluid of the conscious rat. Brain Res 446: 245–250
di Giovine FS, Duff GW (1990) Interleukin-1: the first interleukin. Immunol Today 11: 13–20
Fontana A, Hengartner H, de Tribolet N, Weber E (1984) Glioblastoma cells release interleukin-1 and factors inhibiting interleukin-2 mediated effects. J Immunol 132: 1837–1844
Frei K, Piani D, Malipiero U, Van Meir E, de Tribolet N, Fontana A (1992) Granulocyte-Mecophage colony-stimulating factor (GM-CSF) production by glioblastoma cells. J Immunol 1480: 3140–3146
Gallay P, Carrel S, McDonald HR, Mach JP (1990) Development and comparative analysis of a radioreceptor assay and two solid-phase radioimmunoassays for human IL-1. Experientia 46: A 402
Gallay P, Mach JP, Carrel S (1991) Characterization and detection of naturally occurring antibodies against IL-1α and IL-1β in normal human plasma. Eur Cytokine Netw 2: 329–338
Gearing AJH, Bird CR, Bristow A, Poole S, Thorpe R (1987) A simple sensitive bioassay for interleukin-1 which is unresponsive to 103 U/ml of interleukin-2. J Immunol Methods 99: 7–11
Kasahara T, Mukaida N, Yamashita K, Yagisawa H, Akahoshi T, Matsushima K (1991) IL-1 and TNF-α induction of IL-8 and monocyte chemotactic and activating factor (MCAF) messenger RNA expression in a human astrocytoma cell line. Immunology 74: 60–67
Kasahara T, Yagisawa H, Yamashita K, Yamaguchi Y, Akiyama Y (1990) IL-1 induces proliferation and IL-6 mRNA expression in a human astrocytoma cell line: positive and negative modulation by cholera toxin and cAMP. Biochem Biophys Res Commun 167: 1242–1248
Kuppner MC, Hamou MF, de Tribolet N (1990) Activation and adhesion molecule expression on lymphoid infiltrates in human glioblastomas. J Neuroimmunol 29: 229–238
Kuppner MC, Van Meir E, Hamou MF, de Tribolet N (1990) Cytokine regulation of intercellular adhesion molecule-1 (ICAM-1) expression on human glioblastoma cells. Clin Exp Immunol 81: 142–148
Lachman LB, Brown DC, Dinarello CA (1987) Growth promoting effect of recombinant interleukin-1 and tumour necrosis factor for a human astrocytoma cell line. J Immunol 138: 2913–2916
Larsson I, Landström LE, Larner E, Lundgreen E, Miörner H, Strannegard O (1978) Interferon production in glia and glioma cell lines. Infect Immun 22: 786–789
Lee JC, Simon PL, Young PR (1989) Constitutive and PMA induced interleukin-1 production by the human astrocytoma cell line T 24. Cell Immunol 118: 298–311
Lichtor T, Dohrmann GJ, Gurney ME (1990) Cytokine gene expression by human gliomas. Neurosurgery 26: 788–793
Malipiero UV, Frei K, Fontana A (1990) Production of hemopoietic colony-stimulating factors by astrocytes. J Immunol 144: 3816–3821
Monod L, Diserens AC, Jongeneel CV, Ronco P, Verroust P, de Tribolet N (1989) Human glioma cell lines expressing the common acute lymphoblastic leukaemia antigen (cALLa) have neutral endopeptidase activity. Int J Cancer 44: 948–951
Oppenheim JJ, Kovacs EJ, Matsushima K, Durum SK (1986) There is more than one interleukin-1. Immunol Today 7: 45–55
Piguet V, Carrel S, Diserens AC, Mach JP, de Tribolet N (1986) Heterogeneity of the induction of HLA-DR expression by human immune interferon on glioma cell lines and their clones. J Natl Cancer Inst 76: 223–228
Schwytzer M, Fontana A (1985) Partial purification and biochemical characterization of a T cell suppressor factor produced by human glioblastoma cells. J Immunol 134: 1003–1009
Suda T, Hodgkin P, Lee F, Zlotnik A (1989) Biological activity of recombinant murine interleukin-6 in interleukin-1 T cell assays. J Immunol Methods 120: 173–178
Sundar SK, Becker KJ, Cierpial MA, Carpenter MD, Rankin LA, Fleener SL, Ritchie JC, Simpson PE, Weiss JM (1989) Intracerebroventricular infusion of interleukin-1 rapidly decreases peripheral cellular immune responses. Proc Natl Acad Sci USA 86: 6398–6402
Takiguchi M, Ting JP, Buessow SC, Boyer C, Gillespie Y, Frelinger JA (1985) Response of glioma cells to interferon-γ: increase in class II RNA, protein and mixed lymphocyte reactionstimulating ability. Eur J Immunol 15: 809–814
Van Meir E, Sawamura Y, Diserens AC, Hamou MF, de Tribolet N (1990) Human glioblastoma cells release IL-6in vivo andin vitro. Cancer Res 50: 6683–6688
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gauthier, T., Hamou, M.F., Monod, L. et al. Expression and release of interleukin-1 by human glioblastoma cells in vitro and in vivo. Acta neurochir 121, 199–205 (1993). https://doi.org/10.1007/BF01809276
Issue Date:
DOI: https://doi.org/10.1007/BF01809276