Rolipram impairs NF-kappaB activity and MMP-9 expression in experimental autoimmune encephalomyelitis.

Abstract

Rolipram suppresses experimental autoimmune encephalomyelitis (EAE) and diminishes cell infiltration of the central nervous system (CNS). In Lewis rats with EAE, rolipram reduced matrix metalloproteinase-9 (MMP-9) gene expression in lymph node cells (LNCs) and spinal cord, decreased basal levels of nuclear (p50/p65) NF-kappaB in LNCs from treated rats, and impaired CD3 mediated NF-kappaB translocation. Rolipram reduced the luciferase activity directed by the NF-kappaB binding site of the MMP-9 gene in lymphocytes. It also diminished NF-kappaB activity and the ability of a myelin basic protein (MBP) specific cell line to migrate across artificial basement membranes. IL-2 induced MMP-9 proteolytic activity was only slightly reduced indicating that additional factors contribute to inhibit cell migration mediated by rolipram.