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. 2002 Dec 10;42(1):47–52. doi: 10.1016/0165-5728(93)90211-G

Interleukin-6 induction in vitro in mouse brain endothelial cells and astrocytes by exposure to mouse hepatitis virus (MHV-4, JHM)

Jeymohan Joseph a,∗, James L Grun b, Fred D Lublin a, Robert L Knobler a
PMCID: PMC7119505  PMID: 8380807

Abstract

Interleukin-6 (IL-6) induction, as detected by bioassay and Northern analysis, was examined in vitro in endothelial cells or astrocytes derived from BALB/c (susceptible) or SJL (resistant) mice following exposure to mouse hepatitis virus (MHV-4) or UV inactivated MHV-4 (UV-MHV-4). In BALB/c endothelial cells, up to 16-fold more IL-6 (> 640 U/ml) was induced, compared to SJL cells which showed a minimal response (40 U/ml), relative to basal levels (< 20 U/ml). In contrast, both BALB/c and SJL astrocytes showed a substantial IL-6 response to MHV-4 and UV-MHV-4 exposure, although a strain difference persisted. Despite strain and cell specific differences in released IL-6, equivalent levels of IL-6 mRNA were induced in all cell types following exposure to MHV-4 or UV-MHV-4.

Keywords: Interleukin-6; Mouse hepatis virus (MHV-4, JHM); Cerebral endothelial cells; Astrocytes; Bioassay; Northern analysis

References

  1. Bailey O.T., Pappenheimer A.M., Cheever F.S. A murine virus (JHM) causing disseminated encephalomyelitis with extensive destruction of myelin. Part 2 (Pathology) J. Exp. Med. 1949;90:195–212. doi: 10.1084/jem.90.3.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beneveniste E.N., Sparacio S.M., Norris J.G., Grenett H.E., Fuller G.M. Induction and regulation of interleukin-6 gene expression in rat astrocytes. J. Neuroimmunol. 1990;30:201–212. doi: 10.1016/0165-5728(90)90104-u. [DOI] [PubMed] [Google Scholar]
  3. Borish L., Rosenbaum R., Albury L., Clark S. Activation of neutrophils by recombinant interleukin-6. Cell. Immunol. 1989;121:280–289. doi: 10.1016/0008-8749(89)90026-9. [DOI] [PubMed] [Google Scholar]
  4. Boyle J.F., Weissmiller D.G., Holmes K. Genetic resistance to mouse hepatitis virus correlates with absence of virus binding activity in target tissues. J. Virol. 1987;61:185–189. doi: 10.1128/jvi.61.1.185-189.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Breen E.C., Rezai A.R., Nakajima K., Beall G.N., Mitsuyasu R.T., Hirano T., Kishimoto T., Martinez-Maza O. Infection with HIV is associated with elevated levels of IL-6 production. J. Immunol. 1990;144:480–484. [PubMed] [Google Scholar]
  6. Cernetti C., Steinman R.M., Granelli-Piperno A. Vol. 85. 1988. Identification of a 24kD cytokine that is required for the development of cytolytic T lymphocytes; pp. 1605–1609. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeBault L.E., Henriquez E., Hart M.N., Cancilla P.A. Cerebral microvessel and derived cells in tissue culture. II. Establishment, identification and preliminary characterization of an endothelial cell line. In Vitro. 1981;17:480–494. doi: 10.1007/BF02633509. [DOI] [PubMed] [Google Scholar]
  8. Frei K., Leist T.P., Meager P., Gallo P., Leppert D., Zinkernagel R.M., Fontana A. Production of B-cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. J. Exp. Med. 1988;168:449–453. doi: 10.1084/jem.168.1.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frei K., Malipiero U.V., Leist T.P., Zinkernagel R.M., Schwab M.E., Fontana A. On the cellular source and function of interleukin-6 produced in the central nervous system in viral diseases. Eur. J. Immunol. 1989;19:689–694. doi: 10.1002/eji.1830190418. [DOI] [PubMed] [Google Scholar]
  10. Houssiau F.A., Bukasa K., Sindic C.J.M., Van Damme J., Van Snick J. Elevated levels of a 26K human hybridoma growth factor (interleukin-6) in cerebrospinal fluid of patients with acute infection of the central nervous system. Clin. Exp. Immunol. 1988;71:320–322. [PMC free article] [PubMed] [Google Scholar]
  11. Jayaraman S., Martin C.A., Dorf M.E. Enhancement of in vivo cell mediated immune response by three distinct cytokines. J. Immunol. 1990;144:942–951. [PubMed] [Google Scholar]
  12. Jirik F.R., Podor T.J., Hirano T., Kishimoto T., Loskutoff D.J., Carson D.A., Lotz M. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J. Immunol. 1989;142:144–147. [PubMed] [Google Scholar]
  13. Joseph J., Knobler R.L., Lublin F.D., Hart M.N. Differential modulation of MHC class I antigen expression on mouse brain endothelial cells by MHV-4 infection. J. Neuroimmunol. 1989;22:241–253. doi: 10.1016/0165-5728(89)90022-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Joseph J., Knobler R.L., Lublin F.D., Hart M.N. Regulation of MHC class I and II antigens on cerebral endothelial cells and astrocytes following MHV-4 infection. Adv. Exp. Med. Biol. 1990;276:579–591. doi: 10.1007/978-1-4684-5823-7_80. [DOI] [PubMed] [Google Scholar]
  15. Joseph J., Knobler R.L., Lublin F.D., Hart M.N. Mouse hepatitis virus (MHV-4, JHM) blocks γ-interferon-induced major histocompatility complex class II antigen expression on murine cerebral endothelial cells. J. Neuroimmunol. 1991;33:181–190. doi: 10.1016/0165-5728(91)90105-G. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Knobler R.L., Haspel M.V., Oldstone M.B.A. Mouse hepatitis virus type 4 (JHM strain) induced fatal central nervous system disease. I. Genetic control and the murine neuron as the susceptible site of disease. J. Exp. Med. 1981;153:832–843. doi: 10.1084/jem.153.4.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knobler R.L., Tunison L.A., Lampert P.W., Oldstone M.B.A. Selected mutants of mouse hepatitis virus type 4 (JHM strain) induce different CNS disease. Pathobiology of disease induced by wild type and mutant ts8 and ts15 in BALB/c and SJL mice. Am. J. Pathol. 1982;109:157–168. [PMC free article] [PubMed] [Google Scholar]
  18. Knobler R.L., Cole R., de Vellis J., Lewicki H., Buchmeier M., Oldstone M.B.A. Differential effects of MHV-4 infection of astrocytes and oligodendrocytes in vitro. In: Lai M.M.C., Stohlman S.A., editors. Plenum; New York: 1987. pp. 231–237. (Coronaviruses). [DOI] [PubMed] [Google Scholar]
  19. Le J., Vilcek J. Biology of disease: interleukin-6 a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab. Invest. 1989;61:588–602. [PubMed] [Google Scholar]
  20. Lieberman A.P., Pitha P.M., Shin H.S., Shin M.L. Vol. 86. 1989. Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neutropic virus; pp. 6348–6352. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maniatis T., Fristch E.F., Sambrook J. Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY: 1982. (Molecular Cloning, A Laboratory Manual). [Google Scholar]
  22. McCarthy K.D., deVellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 1980;85:890–902. doi: 10.1083/jcb.85.3.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Natuck R.J., Welsh R.M. Accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication. J. Immunol. 1987;138:877–883. [PubMed] [Google Scholar]
  24. Nishimoto N., Yoshizaki K., Eiraku N., Machigashira K., Tagoh H., Ogata A., Kuritani T., Osame M., Kishimoto T. Elevated levels of interleukin-6 in serum and cerebrospinal fluid of HTLV-1 associated myelophathy/tropical spastic paraparesis. J. Neurol. Sci. 1990;97:183–193. doi: 10.1016/0022-510x(90)90217-b. [DOI] [PubMed] [Google Scholar]
  25. Sahagun G., Moore S.A., Fabry Z., Schelpher R.L., Hart M.N. Purification of murine endothelial cell cultures by flow cytometry using fluorescein-labeled Griffonia simplicifolia agglutinin. Am. J. Pathol. 1989;134:1227–1232. [PMC free article] [PubMed] [Google Scholar]
  26. Shalaby M.R., Waage A., Esperik T. Cytokine regulation of interleukin-6 production by human endothelial cells. Cell. Immunol. 1989;121:372–382. doi: 10.1016/0008-8749(89)90036-1. [DOI] [PubMed] [Google Scholar]
  27. Sironi M., Brevario F., Prosperio P., Biondi A., Vecchi A., Van Damme J., Dejana E., Mantovani A. IL-1 stimulates IL-6 production by endothelial cells. J. Immunol. 1989;142:549–553. [PubMed] [Google Scholar]
  28. Stohlman S.A., Brayton P.R., Harmon R.C., Stevenson R.G., Ganges R.G., Matsushima G.K. Natural killer cell activity during mouse hepatitis virus infection: response in the absence of interferon. Int. J. Cancer. 1983;31:309–314. doi: 10.1002/ijc.2910310310. [DOI] [PubMed] [Google Scholar]
  29. Suzuki K., Kawakami M., Tabata H., Kawagoe M., Nakamura H. Production of B cell stimulatory factor-2/interleukin-6 activity by human endothelial cells. Biochem. Biophys. Res. Commun. 1988;153:1045–1049. doi: 10.1016/s0006-291x(88)81334-2. [DOI] [PubMed] [Google Scholar]
  30. Takai Y., Wong G.G., Clark S.C., Burakoff S.J., Hermann S.H. B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J. Immunol. 1988;140:508–512. [PubMed] [Google Scholar]
  31. Uttenhove C., Coulie P.G., Van Snick J. T-cell growth and differentiation induced by interleukin-1, the murine hybridoma plasmacytoma growth factor. J. Exp. Med. 1988;167:1417–1427. doi: 10.1084/jem.167.4.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Voyta J.C., Netland P.A., Via D.P., Zetter B.R. Specific labeling of endothelial cells using fluorescent acetylated low density lipoprotein. J. Cell Biol. 1984;99:81A. doi: 10.1083/jcb.99.6.2034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wang F.-I., Stohlman S.A., Fleming J.O. Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated. J. Neuroimmunol. 1990;30:31–34. doi: 10.1016/0165-5728(90)90050-W. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Welsh R.M., Haspel M.V., Parker D.C., Holmes K.V. Natural cytotoxicity against mouse hepatitis virus-infected cells. II. A cytotoxic effector cell with a B lymphocyte phenotype. J. Immunol. 1986;136:1454–1460. [PubMed] [Google Scholar]
  35. Williams R.K., Jiang G.S., Snyder S.W., Frana M.F., Holmes K.V. Purification of the 110-kD glycoprotein receptor for MHV-A59 from mouse liver and identification of a non-functional homologous protein in M MHV-resistant SJL/J mice. J. Virol. 1990;64:3817–3823. doi: 10.1128/jvi.64.8.3817-3823.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Williamson J.S.P., Sykes K.C., Stohlman S.A. Characterization of brain-infiltrating mononuclear cells during infection with mouse hepatitis virus strain JHM. J. Neuroimmunol. 1991;32:199–207. doi: 10.1016/0165-5728(91)90189-E. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zimprich F., Winter J., Wege H., Lassmann H. Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response. Neuropathol. Appl. Neurobiol. 1991;17:469–484. doi: 10.1111/j.1365-2990.1991.tb00750.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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