5HT4 agonists inhibit interferon-γ-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-HT4 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-HT4 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-HT4 agonists may have therapeutic potential in multiple sclerosis by inhibiting the up-regulation of immune responsiveness of astrocytes in the central nervous system. (c) 2006 Elsevier B.V. All rights reserved.