Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus.
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.
Lieberman
A P
AP
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Pitha
P M
PM
Shin
H S
HS
Shin
M L
ML
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001685:Biological Factors / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D016207:Cytokines; D005260:Female; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology; D009522:Newcastle disease virus / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D001685:Biological Factors; D016207:Cytokines; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons