Norepinephrine inhibits gamma-interferon-induced major histocompatibility class II (Ia) antigen expression on cultured astrocytes via beta-2-adrenergic signal transduction mechanisms.
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 gamma 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 beta-adrenergic antagonist, propranolol, but not by the addition of a beta 1-selective antagonist, atenolol, or by an alpha-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 beta 2-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.
Frohman
E M
EM
Department of Neurology, University of California, Irvine 92717.
Vayuvegula
B
B
Gupta
S
S
van den Noort
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology; D001262:Atenolol / Q000494:pharmacology; D001921:Brain / Q000276:immunology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D000949:Histocompatibility Antigens Class II; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D003994:Bucladesine; D004176:Dipyridamole; D007371:Interferon-gamma; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D010646:Phentolamine