5HT(4) agonists inhibit interferon-gamma-induced MHC class II and B7 costimulatory molecules expression on cultured astrocytes

Esther M. Zeinstra, Nadine Wilczak, Jan C. Wilschut, Lisa Glazenburg, Daniel Chesik, Frans G. M. Kroese, Jacques De Keyser*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)191-195
Number of pages5
JournalJournal of Neuroimmunology
Volume179
Issue number1-2
DOIs
Publication statusPublished - Oct-2006

Keywords

  • MHC class II
  • astrocytes
  • B7 co-stimulatory molecules
  • cAMP
  • 5-HT4 agonists
  • multiple sclerosis
  • CENTRAL-NERVOUS-SYSTEM
  • MULTIPLE-SCLEROSIS
  • IA-ANTIGEN
  • RECEPTORS
  • CELLS
  • PLAQUES
  • LESIONS
  • TISSUE

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