5HT4 agonists inhibit interferon-gamma-induced MHC class II and B7 costimulatory molecules expression on cultured astrocytes.
A failure of tight control of MHC class II expression on astrocytes may play a role in the development of autoimmune responses in multiple sclerosis. The 5-HT(4) serotonin receptor agonists cisapride and prucalopride, at concentrations between 10(-10) M and 10(-8) M, reduced interferon-gamma-induced MHC class II immunostaining in cultured astrocytes derived from newborn Wistar rats by approximately 50-60%. The magnitude of MHC class II inhibition by 5-HT(4) agonists was comparable to that of interferon-beta. The alpha(1)-adrenergic receptor agonist phenylephrine was without effect. Cisapride (10(-9) M) also prevented interferon-gamma-induced B7-1 and B7-2 immunostaining. Our results suggest that 5-HT(4) agonists may have therapeutic potential in multiple sclerosis by inhibiting the up-regulation of immune responsiveness of astrocytes in the central nervous system.
Zeinstra
Esther M
EM
Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands.
Wilczak
Nadine
N
Wilschut
Jan C
JC
Glazenburg
Lisa
L
Chesik
Daniel
D
Kroese
Frans G M
FG
De Keyser
Jacques
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D001572:Benzofurans / Q000494:pharmacology; D002478:Cells, Cultured; D020117:Cisapride / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D018122:B7-1 Antigen; D001572:Benzofurans; D000949:Histocompatibility Antigens Class II; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C406662:prucalopride; D010656:Phenylephrine; D007371:Interferon-gamma; D020117:Cisapride