Norepinephrine inhibits γ interferon-induced major histocompatibility class II (Ia) antigen expression on cultured astrocytes via β2-adrenergic signal transduction mechanisms

Elliot Frohman, B. Vayuvegula, S. Gupta, S. Van Den Noort

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Abstract

The astrocyte is now recognized as a facultative immunocompetent antigen-presenting cell that can initiate intracerebral immune responses. However, despite the presence of activated T lymphocytes and their associated lymphokines within the central nervous system, there is a paucity in the expression of the major histocompatibility (MHC) antigens on normal neural tissue. These membrane-localized glycoproteins are required for the process of antigen presentation and, therefore, for the initiation of immune responses. To date, little is understood regarding the nature of inhibitory mechanisms that might be responsible for maintaining the brain as an immunoprivileged site. In this study we found that norepinephrine, a major brain transmitter, significantly inhibited γ interferon-induced MHC class II antigen expression on astrocytes derived from neonatal Lewis rats. We show that this inhibition can be attenuated by the addition of a β-adrenergic antagonist, propranolol, but not by the addition of a β1-selective antagonist, atenolol, or by an α-adrenergic antagonist, phentolamine. Furthermore, it was found that a similar inhibition could be achieved by the addition of either dibutyryl-cAMP or dipyridimole, a phosphodiesterase inhibitor. Therefore, it seems that norepinephrine-mediated inhibition of MHC class II antigen expression on astrocytes works through β2-adrenergic signal transduction pathways. Taken together, these in vitro results suggest that the brain contains inhibitory factors that may play a pivotal role in the regulation of intracerebral immune responses by modulating the expression of MHC antigens on astrocytes.

Original languageEnglish (US)
Pages (from-to)1292-1296
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number4
DOIs
StatePublished - Jan 1 1988

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