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. 1993 Aug;143(2):337–341.

Interleukin-4 down-regulates adult human astrocyte DNA synthesis and proliferation.

M L Estes 1, K Iwasaki 1, B S Jacobs 1, B P Barna 1
PMCID: PMC1887009  PMID: 8342591

Abstract

The T lymphocyte-derived cytokine, interleukin-4 (IL-4), was found to inhibit dose dependently basal DNA synthesis of cultured non-neoplastic human astrocytes isolated from epilepsy white matter tissue. The mitogenic effect of tumor necrosis factor on astrocytes was also inhibited by IL-4, and the inhibitory effect was abrogated by anti-IL-4 antibody but not by irrelevant IgG. Immunofluorescent analysis indicated significantly reduced numbers of glial fibrillary acidic protein-positive astrocytes incorporating nuclear bromodeoxyuridine in IL-4-treated cultures compared to control. These findings indicate that human adult astrocyte proliferation, in contrast to that reported for endothelial cells or fibroblasts, is sensitive to down-regulation by IL-4.

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Selected References

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  1. Barna B. P., Chou S. M., Jacobs B., Yen-Lieberman B., Ransohoff R. M. Interferon-beta impairs induction of HLA-DR antigen expression in cultured adult human astrocytes. J Neuroimmunol. 1989 Jun;23(1):45–53. doi: 10.1016/0165-5728(89)90072-6. [DOI] [PubMed] [Google Scholar]
  2. Barna B. P., Estes M. L., Jacobs B. S., Hudson S., Ransohoff R. M. Human astrocytes proliferate in response to tumor necrosis factor alpha. J Neuroimmunol. 1990 Dec;30(2-3):239–243. doi: 10.1016/0165-5728(90)90108-y. [DOI] [PubMed] [Google Scholar]
  3. Booss J., Esiri M. M., Tourtellotte W. W., Mason D. Y. Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis. J Neurol Sci. 1983 Dec;62(1-3):219–232. doi: 10.1016/0022-510x(83)90201-0. [DOI] [PubMed] [Google Scholar]
  4. Essner R., Rhoades K., McBride W. H., Morton D. L., Economou J. S. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol. 1989 Jun 1;142(11):3857–3861. [PubMed] [Google Scholar]
  5. Estes M. L., Ransohoff R. M., McMahon J. T., Jacobs B. S., Barna B. P. Characterization of adult human astrocytes derived from explant culture. J Neurosci Res. 1990 Dec;27(4):697–705. doi: 10.1002/jnr.490270430. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Giulian D., Lachman L. B. Interleukin-1 stimulation of astroglial proliferation after brain injury. Science. 1985 Apr 26;228(4698):497–499. doi: 10.1126/science.3872478. [DOI] [PubMed] [Google Scholar]
  8. Hauser S. L., Bhan A. K., Gilles F., Kemp M., Kerr C., Weiner H. L. Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol. 1986 Jun;19(6):578–587. doi: 10.1002/ana.410190610. [DOI] [PubMed] [Google Scholar]
  9. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee H. K., Xia X., Choi Y. S. IL-4 blocks the up-regulation of IL-2 receptors induced by IL-2 in normal human B cells. J Immunol. 1990 May 1;144(9):3431–3436. [PubMed] [Google Scholar]
  11. Merrill J. E., Kutsunai S., Mohlstrom C., Hofman F., Groopman J., Golde D. W. Proliferation of astroglia and oligodendroglia in response to human T cell-derived factors. Science. 1984 Jun 29;224(4656):1428–1430. doi: 10.1126/science.6610212. [DOI] [PubMed] [Google Scholar]
  12. Monroe J. G., Haldar S., Prystowsky M. B., Lammie P. Lymphokine regulation of inflammatory processes: interleukin-4 stimulates fibroblast proliferation. Clin Immunol Immunopathol. 1988 Nov;49(2):292–298. doi: 10.1016/0090-1229(88)90119-5. [DOI] [PubMed] [Google Scholar]
  13. Morisaki T., Yuzuki D. H., Lin R. T., Foshag L. J., Morton D. L., Hoon D. S. Interleukin 4 receptor expression and growth inhibition of gastric carcinoma cells by interleukin 4. Cancer Res. 1992 Nov 1;52(21):6059–6065. [PubMed] [Google Scholar]
  14. Mosmann T. R., Bond M. W., Coffman R. L., Ohara J., Paul W. E. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654–5658. doi: 10.1073/pnas.83.15.5654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  16. Salgame P., Abrams J. S., Clayberger C., Goldstein H., Convit J., Modlin R. L., Bloom B. R. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991 Oct 11;254(5029):279–282. doi: 10.1126/science.254.5029.279. [DOI] [PubMed] [Google Scholar]
  17. Selmaj K. W., Farooq M., Norton W. T., Raine C. S., Brosnan C. F. Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol. 1990 Jan 1;144(1):129–135. [PubMed] [Google Scholar]
  18. Spits H., Yssel H., Paliard X., Kastelein R., Figdor C., de Vries J. E. IL-4 inhibits IL-2-mediated induction of human lymphokine-activated killer cells, but not the generation of antigen-specific cytotoxic T lymphocytes in mixed leukocyte cultures. J Immunol. 1988 Jul 1;141(1):29–36. [PubMed] [Google Scholar]
  19. Stuart P. M., Zlotnik A., Woodward J. G. Induction of class I and class II MHC antigen expression on murine bone marrow-derived macrophages by IL-4 (B cell stimulatory factor 1). J Immunol. 1988 Mar 1;140(5):1542–1547. [PubMed] [Google Scholar]
  20. Toi M., Bicknell R., Harris A. L. Inhibition of colon and breast carcinoma cell growth by interleukin-4. Cancer Res. 1992 Jan 15;52(2):275–279. [PubMed] [Google Scholar]
  21. Toi M., Harris A. L., Bicknell R. Interleukin-4 is a potent mitogen for capillary endothelium. Biochem Biophys Res Commun. 1991 Feb 14;174(3):1287–1293. doi: 10.1016/0006-291x(91)91561-p. [DOI] [PubMed] [Google Scholar]
  22. Tracey K. J., Morgello S., Koplin B., Fahey T. J., 3rd, Fox J., Aledo A., Manogue K. R., Cerami A. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. J Clin Invest. 1990 Dec;86(6):2014–2024. doi: 10.1172/JCI114937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Traugott U., Reinherz E. L., Raine C. S. Multiple sclerosis. Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages. J Neuroimmunol. 1983 Jun;4(3):201–221. doi: 10.1016/0165-5728(83)90036-x. [DOI] [PubMed] [Google Scholar]
  24. Widmer M. B., Acres R. B., Sassenfeld H. M., Grabstein K. H. Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor 1 (interleukin 4). J Exp Med. 1987 Nov 1;166(5):1447–1455. doi: 10.1084/jem.166.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yong V. W., Moumdjian R., Yong F. P., Ruijs T. C., Freedman M. S., Cashman N., Antel J. P. Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7016–7020. doi: 10.1073/pnas.88.16.7016. [DOI] [PMC free article] [PubMed] [Google Scholar]

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