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

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-κB in LNCs from treated rats, and impaired CD3 mediated NF-κB translocation. Rolipram reduced the luciferase activity directed by the NF-κB binding site of the MMP-9 gene in lymphocytes. It also diminished NF-κB 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.