Induction of RANTES expression by astrocytes and astrocytoma cell lines.
The cellular infiltrate found during the acute phase of multiple sclerosis (MS) consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during the inflammatory response. We examined the ability of human astrocytoma cell lines, as well as primary human and rat astrocytes, to generate a specific member of the intercrine/chemokine family of cytokines, RANTES, when exposed to TNF-alpha, IL-1 beta and IFN-gamma. Astrocytoma cells as well as primary astrocytes produced RANTES upon incubation with TNF-alpha or IL-1 beta. IFN-gamma alone did not induce RANTES production by astrocytes, but it potentiated the effects of either TNF-alpha or IL-1 beta. Induction of RANTES by TNF-alpha was mediated by the p55 receptor since a specific anti-p55 antiserum mimicked the effect of TNF-alpha. These results indicate that human astrocytes are capable of generating a cell-specific chemokine that can account for the inflammatory cellular infiltrate observed during the acute phase of MS, in a process that is regulated by cytokines.
Barnes
D A
DA
Department of Immunology, Berlex Biosciences, Richmond, CA 94804, USA.
Huston
M
M
Holmes
R
R
Benveniste
E N
EN
Yong
V W
VW
Scholz
P
P
Perez
H D
HD
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018946:Chemokine CCL5; D007375:Interleukin-1; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma