Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1997 Aug;91(4):560–564. doi: 10.1046/j.1365-2567.1997.00305.x

Interferon-gamma induces the expression of immediate early genes c-fos and c-jun in astrocytes.

N Rubio 1
PMCID: PMC1363876  PMID: 9378495

Abstract

The expression of the proto-oncogenes, c-fos and c-jun, in cultured mouse astrocytes and its induction by the potent astrocyte activator interferon-gamma (IFN-gamma), were examined by Northern blot and flow cytometry. Both proto-oncogenes were induced in a dose-dependent manner, peaking around 100 U/ml of IFN-gamma. The kinetics of expression is very transient for c-fos, reaching a maximum at 30 min and decreasing rapidly thereafter. The c-jun remained high throughout the stages analysed. Cycloheximide superinduced c-fos and c-jun induction by IFN-gamma, thus indicating that both act as immediate early genes. The products of c-fos and c-jun, proteins FOS and JUN, that act in conjunction forming the regulatory factor AP-1, were detected 1 hr after stimulation in virtually all cells, using flow cytometry. The induction in astrocytes of both proto-oncogenes could be the first stage of immunological activation of these central nervous system cells by immune interferon.

Full text

PDF
560

Images in this article

561Figure 1
on p.561
562Figure 2
on p.562
562Figure 3
on p.562
562Figure 4
on p.562
562Figure 5
on p.562

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arenander A. T., de Vellis J., Herschman H. R. Induction of c-fos and TIS genes in cultured rat astrocytes by neurotransmitters. J Neurosci Res. 1989 Sep;24(1):107–114. doi: 10.1002/jnr.490240115. [DOI] [PubMed] [Google Scholar]
  2. Brenner D. A., O'Hara M., Angel P., Chojkier M., Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989 Feb 16;337(6208):661–663. doi: 10.1038/337661a0. [DOI] [PubMed] [Google Scholar]
  3. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  4. Curran T., Peters G., Van Beveren C., Teich N. M., Verma I. M. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. doi: 10.1128/jvi.44.2.674-682.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dragunow M., Currie R. W., Robertson H. A., Faull R. L. Heat shock induces c-fos protein-like immunoreactivity in glial cells in adult rat brain. Exp Neurol. 1989 Oct;106(1):105–109. doi: 10.1016/0014-4886(89)90152-0. [DOI] [PubMed] [Google Scholar]
  6. Dragunow M., Robertson H. A. Brain injury induces c-fos protein(s) in nerve and glial-like cells in adult mammalian brain. Brain Res. 1988 Jul 12;455(2):295–299. doi: 10.1016/0006-8993(88)90088-1. [DOI] [PubMed] [Google Scholar]
  7. Fierz W., Endler B., Reske K., Wekerle H., Fontana A. Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation. J Immunol. 1985 Jun;134(6):3785–3793. [PubMed] [Google Scholar]
  8. Fontana A., Fierz W., Wekerle H. Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature. 1984 Jan 19;307(5948):273–276. doi: 10.1038/307273a0. [DOI] [PubMed] [Google Scholar]
  9. Fu L., Beckstead R. M. Cortical stimulation induces fos expression in striatal neurons. Neuroscience. 1992;46(2):329–334. doi: 10.1016/0306-4522(92)90055-7. [DOI] [PubMed] [Google Scholar]
  10. Fujita S. C., Zipursky S. L., Benzer S., Ferrús A., Shotwell S. L. Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7929–7933. doi: 10.1073/pnas.79.24.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. González-Martín C., de Diego I., Fairén A., Mellström B., Naranjo J. R. Transient expression of c-fos during the development of the rat cerebral cortex. Brain Res Dev Brain Res. 1991 Mar 18;59(1):109–112. doi: 10.1016/0165-3806(91)90036-i. [DOI] [PubMed] [Google Scholar]
  12. Hatakeyama M., Kawahara A., Mori H., Shibuya H., Taniguchi T. c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2022–2026. doi: 10.1073/pnas.89.6.2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hilberg F., Aguzzi A., Howells N., Wagner E. F. c-jun is essential for normal mouse development and hepatogenesis. Nature. 1993 Sep 9;365(6442):179–181. doi: 10.1038/365179a0. [DOI] [PubMed] [Google Scholar]
  14. Hirsch M. R., Wietzerbin J., Pierres M., Goridis C. Expression of Ia antigens by cultured astrocytes treated with gamma-interferon. Neurosci Lett. 1983 Oct 31;41(1-2):199–204. doi: 10.1016/0304-3940(83)90247-1. [DOI] [PubMed] [Google Scholar]
  15. Hughes P., Lawlor P., Dragunow M. Basal expression of Fos, Fos-related, Jun, and Krox 24 proteins in rat hippocampus. Brain Res Mol Brain Res. 1992 May;13(4):355–357. doi: 10.1016/0169-328x(92)90219-2. [DOI] [PubMed] [Google Scholar]
  16. Körholz D., Gerdau S., Enczmann J., Zessack N., Burdach S. Interleukin 6-induced differentiation of a human B cell line into IgM-secreting plasma cells is mediated by c-fos. Eur J Immunol. 1992 Feb;22(2):607–610. doi: 10.1002/eji.1830220248. [DOI] [PubMed] [Google Scholar]
  17. Lau L. F., Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182–1186. doi: 10.1073/pnas.84.5.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Majumder S., Zhou L. Z., Ransohoff R. M. Transcriptional regulation of chemokine gene expression in astrocytes. J Neurosci Res. 1996 Sep 15;45(6):758–769. doi: 10.1002/(SICI)1097-4547(19960915)45:6<758::AID-JNR12>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  19. Morgan J. I., Curran T. Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci. 1991;14:421–451. doi: 10.1146/annurev.ne.14.030191.002225. [DOI] [PubMed] [Google Scholar]
  20. Neumann H., Boucraut J., Hahnel C., Misgeld T., Wekerle H. Neuronal control of MHC class II inducibility in rat astrocytes and microglia. Eur J Neurosci. 1996 Dec;8(12):2582–2590. doi: 10.1111/j.1460-9568.1996.tb01552.x. [DOI] [PubMed] [Google Scholar]
  21. Panitch H. S., Hirsch R. L., Schindler J., Johnson K. P. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology. 1987 Jul;37(7):1097–1102. doi: 10.1212/wnl.37.7.1097. [DOI] [PubMed] [Google Scholar]
  22. Rubio N., Cuesta A. Lack of cross-reaction between myelin basic proteins and putative demyelinating virus envelope proteins. Mol Immunol. 1989 Jul;26(7):663–668. doi: 10.1016/0161-5890(89)90049-7. [DOI] [PubMed] [Google Scholar]
  23. Rubio N., De Felipe C., Torres C. Theiler's murine encephalomyelitis virus-binding activity on neural and non-neural cell lines and tissues. J Gen Virol. 1990 Dec;71(Pt 12):2867–2872. doi: 10.1099/0022-1317-71-12-2867. [DOI] [PubMed] [Google Scholar]
  24. Rubio N., Rojo P., Torres C. Overexpression of basal c-fos and c-jun but not of ras oncogenes after Theiler's murine encephalomyelitis virus infection of glial cells. J Neurovirol. 1996 Jun;2(3):167–174. doi: 10.3109/13550289609146879. [DOI] [PubMed] [Google Scholar]
  25. Ryseck R. P., Hirai S. I., Yaniv M., Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. doi: 10.1038/334535a0. [DOI] [PubMed] [Google Scholar]
  26. Sassone-Corsi P., Ransone L. J., Lamph W. W., Verma I. M. Direct interaction between fos and jun nuclear oncoproteins: role of the 'leucine zipper' domain. Nature. 1988 Dec 15;336(6200):692–695. doi: 10.1038/336692a0. [DOI] [PubMed] [Google Scholar]
  27. Shrikant P., Benveniste E. N. The central nervous system as an immunocompetent organ: role of glial cells in antigen presentation. J Immunol. 1996 Sep 1;157(5):1819–1822. [PubMed] [Google Scholar]
  28. Smeyne R. J., Vendrell M., Hayward M., Baker S. J., Miao G. G., Schilling K., Robertson L. M., Curran T., Morgan J. I. Continuous c-fos expression precedes programmed cell death in vivo. Nature. 1993 May 13;363(6425):166–169. doi: 10.1038/363166a0. [DOI] [PubMed] [Google Scholar]
  29. Torres C., Aránguez I., Rubio N. Expression of interferon-gamma receptors on murine oligodendrocytes and its regulation by cytokines and mitogens. Immunology. 1995 Oct;86(2):250–255. [PMC free article] [PubMed] [Google Scholar]
  30. Vanguri P., Farber J. M. IFN and virus-inducible expression of an immediate early gene, crg-2/IP-10, and a delayed gene, I-A alpha in astrocytes and microglia. J Immunol. 1994 Feb 1;152(3):1411–1418. [PubMed] [Google Scholar]
  31. Wong G. H., Bartlett P. F., Clark-Lewis I., McKimm-Breschkin J. L., Schrader J. W. Interferon-gamma induces the expression of H-2 and Ia antigens on brain cells. J Neuroimmunol. 1985 Feb-Mar;7(5-6):255–278. doi: 10.1016/s0165-5728(84)80026-0. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES