Type IV phosphodiesterase inhibition in experimental allergic encephalomyelitis of Lewis rats: Sequential gene expression analysis of cytokines, adhesion molecules and the inducible nitric oxide synthase

Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis

“…Activation/suppression of APCs and regulation of the cytokine environment are known to be controlled by cAMP levels (Fassbender et al, 2010;Kambayashi et al, 2001). Therefore the upregulation of PDE4B2 mRNA that we report here, in areas with high amount of cellular infiltrates and around the microvessels, together with the role of cAMP in the antigen presentation process (Fallarino et al, 2010) The amelioration of the clinical signs and delayed onset of EAE described after PDE4 inhibition (Folcik et al, 1999;Martinez et al, 1999;Moore et al, 2006;Sommer et al, 1995) T-cell populations that have a crucial role in the EAE model are Th1-and Th17-positive cells (Komiyama et al, 2006;Tzartos et al, 2008;Zamvil and Steinman 1990). These immune cells infiltrate and attack oligodendrocytes, activate resident microglia and astrocytes, leading to demyelination and axonal damage in the EAE model (Lassmann et al, 2001;Soulika et al, 2009).…”

Suppression of encephalitogenic T-cell responses by cilostazol is associated with upregulation of regulatory T cells

“…Several PDE inhibitors have been documented to exert inhibitory effects on immune responses [4,5,14]. Although the capacity of cilostazol to inhibit cell proliferation and adhesive molecule expression has been well established in nonimmune cells, the effect of cilostazol on the immune system is poorly understood.…”

“…Several therapeutic strategies for improving clinical outcomes of EAE/MS have been tried, including the use of immunosuppressive drugs or cytokines to inhibit T-cell responses, induction of immunological tolerance to autoantigens, and administration of anti-inflammatory drugs, such as PDE inhibitors to reduce inflammation in CNS [4,14]. Kureshiro et al [7] recently showed that oral administration of cilostazol ameliorates EAE by inhibiting proliferation and interferon (IFN)-g production by autoreactive T cells.…”

The Antidepressant and Antiinflammatory Effects of Rolipram in the Central Nervous System

“…It can suppress the acute and chronic clinical symptoms of EAE (2,25,27,36,45,69,70). Agnello et al (2) studied the mRNA expression of pentraxin 3 (PTX3) and the binding of the peripheraltype benzodiazepine receptor (PBR) ligand [ 3 H]PK11195 in the spinal cord of Lewis rats with actively induced EAE.…”