Production of Tumor Necrosis Factor and Other Cytokines by Astrocytes Stimulated with Lipopolysaccharide or a Neurotropic Virus

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1989 Aug 1

PMID 2474832

Citations 167

Authors

A P Lieberman

P M Pitha

H S Shin

M L Shin

Affiliations

Soon will be listed here.

Abstract

Rat astrocytes, immunologically competent glial cells of the central nervous system (CNS), released a variety of cytokines after activation. Lipopolysaccharide-stimulated astrocytes produced tumor necrosis factor (TNF) as demonstrated by Northern blot analysis using a mouse TNF probe and by functional assay. Biological activity of rat astrocyte-derived TNF was neutralized by rabbit antiserum against recombinant murine TNF. Stimulation of astrocytes by lipopolysaccharide also activated the interleukin 1 and interleukin 6 genes. We have also investigated whether a neurotropic paramyxovirus, Newcastle disease virus, triggers cytokine production by astrocytes. This virus induced astrocytes to produce TNF, lymphotoxin, interleukin 6, and alpha- and beta-interferons. Thus, stimulation by endotoxin and virus activated distinct, yet overlapping, sets of cytokine genes. We propose that astrocytes and the cytokines they produce may play a significant role in the pathogenesis of immunologically and/or virally mediated CNS disease, in CNS intercellular communication, and in the interactions between the nervous and immune systems.

Citing Articles

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy.

Chen X, Chen S, Lai X, Fu J, Yang J, Ou R Front Cell Neurosci. 2024; 18:1459884.

PMID: 39295596 PMC: 11409425. DOI: 10.3389/fncel.2024.1459884.

Chronic Astrocytic TNFα Production in the Preoptic-Basal Forebrain Causes Aging-like Sleep-Wake Disturbances in Young Mice.

Kostin A, Alam M, Saevskiy A, Alam M Cells. 2024; 13(11.

PMID: 38891027 PMC: 11171867. DOI: 10.3390/cells13110894.

Elucidating the Therapeutic Utility of Olaparib in Sulfatide-Induced Human Astrocyte Toxicity and Neuroinflammation.

Mekhaeil M, Conroy M, Dev K J Neuroimmune Pharmacol. 2023; 18(4):592-609.

PMID: 37924373 PMC: 10770269. DOI: 10.1007/s11481-023-10092-9.

Immunity impacts cognitive deficits across neurological disorders.

Shaw B, Anders V, Tinkey R, Habean M, Brock O, Frostino B J Neurochem. 2023; 168(10):3512-3535.

PMID: 37899543 PMC: 11056485. DOI: 10.1111/jnc.15999.

New insight into neurological degeneration: Inflammatory cytokines and blood-brain barrier.

Yang J, Ran M, Li H, Lin Y, Ma K, Yang Y Front Mol Neurosci. 2022; 15:1013933.

PMID: 36353359 PMC: 9637688. DOI: 10.3389/fnmol.2022.1013933.

References

Chirgwin J, Przybyla A, MacDonald R, Rutter W . Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979; 18(24):5294-9. DOI: 10.1021/bi00591a005. View

Massa P, Ter Meulen V, Fontana A . Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1987; 84(12):4219-23. PMC: 305056. DOI: 10.1073/pnas.84.12.4219. View

Johnson R . Viruses and chronic neurological diseases. Johns Hopkins Med J. 1982; 150(4):132-40. View

Raj N, Pitha P . Analysis of interferon mRNA in human fibroblast cells induced to produce interferon. Proc Natl Acad Sci U S A. 1981; 78(12):7426-30. PMC: 349280. DOI: 10.1073/pnas.78.12.7426. View

Fontana A, Kristensen F, Dubs R, Gemsa D, Weber E . Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982; 129(6):2413-9. View

Koski C, Ramm L, HAMMER C, Mayer M, Shin M . Cytolysis of nucleated cells by complement: cell death displays multi-hit characteristics. Proc Natl Acad Sci U S A. 1983; 80(12):3816-20. PMC: 394143. DOI: 10.1073/pnas.80.12.3816. View

HIRSCH M, Wietzerbin J, Pierres M, Goridis C . Expression of Ia antigens by cultured astrocytes treated with gamma-interferon. Neurosci Lett. 1983; 41(1-2):199-204. DOI: 10.1016/0304-3940(83)90247-1. View

HARPER H, Pitha P . Effect of concanavalin A on interferon induction by poly IC. Biochem Biophys Res Commun. 1973; 53(4):1220-6. DOI: 10.1016/0006-291x(73)90595-0. View

Rigby P, Dieckmann M, Rhodes C, Berg P . Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977; 113(1):237-51. DOI: 10.1016/0022-2836(77)90052-3. View

10.

Fontana A, Fierz W, Wekerle H . Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature. 1984; 307(5948):273-6. DOI: 10.1038/307273a0. View

11.

Wong G, Bartlett P, Clark-Lewis I, Battye F, Schrader J . Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984; 310(5979):688-91. DOI: 10.1038/310688a0. View

12.

Melton D, Krieg P, Rebagliati M, Maniatis T, Zinn K, Green M . Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984; 12(18):7035-56. PMC: 320141. DOI: 10.1093/nar/12.18.7035. View

13.

Fujita T, Ohno S, Yasumitsu H, Taniguchi T . Delimitation and properties of DNA sequences required for the regulated expression of human interferon-beta gene. Cell. 1985; 41(2):489-96. DOI: 10.1016/s0092-8674(85)80022-2. View

14.

Ryals J, Dierks P, Ragg H, Weissmann C . A 46-nucleotide promoter segment from an IFN-alpha gene renders an unrelated promoter inducible by virus. Cell. 1985; 41(2):497-507. DOI: 10.1016/s0092-8674(85)80023-4. View

15.

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; 134(6):3785-93. View

16.

Waksman B . Mechanisms in multiple sclerosis. Nature. 1985; 318(6042):104-5. DOI: 10.1038/318104a0. View

17.

Frei K, Bodmer S, Schwerdel C, Fontana A . Astrocytes of the brain synthesize interleukin 3-like factors. J Immunol. 1985; 135(6):4044-7. View

18.

Aderka D, Holtmann H, Toker L, Hahn T, Wallach D . Tumor necrosis factor induction by Sendai virus. J Immunol. 1986; 136(8):2938-42. View

19.

Beutler B, Krochin N, Milsark I, Luedke C, Cerami A . Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986; 232(4753):977-80. DOI: 10.1126/science.3754653. View

20.

Suzumura A, Lavi E, Weiss S, Silberberg D . Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes. Science. 1986; 232(4753):991-3. DOI: 10.1126/science.3010460. View