TNF-alpha and IL-1beta cross-desensitization of astrocytes and astrocytoma cell lines.
Exposure of human astrocytes and astrocytoma cell lines to TNF-alpha, IL-1beta and gammaIFN induce expression of a specific member of the intercrine/chemokine family of cytokines, RANTES. Pre-incubation with non-stimulatory concentrations of TNF-alpha inhibit IL-1beta-stimulated RANTES expression and similarly, non-stimulatory concentrations of IL-1beta inhibits TNF-alpha induced RANTES expression. The lowered responsiveness of these cells is stably maintained for at least 24 h. The inhibitory effect of TNF-alpha on IL-1beta-induced responses was mediated by TNF receptor-1 since low concentrations of a specific anti-TNF receptor-1 antiserum mimicked the inhibitory effect. These results indicate that TNF and IL-1 receptors mediate pro- and antiinflammatory responses in a concentration dependent manner, suggesting that at low receptor occupancy, TNF and IL-1 receptors may share a common signaling pathway and behave as endogenous antiinflammatory cytokines.
Department of Immunology, Berlex Biosciences, Richmond, CA 94804, USA. debra_barnes@berlex.com
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Barnes
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Huston
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Perez
D001253:Astrocytes / Q000187:drug effects*; D001254:Astrocytoma / Q000473:pathology*; D002460:Cell Line / Q000187:drug effects; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D009994:Osmolar Concentration; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018946:Chemokine CCL5; D007375:Interleukin-1; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma