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Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development
Akio Suzumura1, Atsushi Ito, Tetsuya Mizuno
1Department of Neuroimmunology, Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan. suzumura@riem.nagoya-u.ac.jp
The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (CNS), were examined to learn how they affect T cell differentiation in the CNS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-polymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional heterodimer, p70. In addition, the PDEI ibudilast also suppressed interferon-gamma, but not IL-4 or IL-10, production by myelin oligodendrocyte glycoprotein (MOG)-specific T cells reactivated with MOG in the presence of microglia. Thus, PDEIs may also suppress differentiation of T helper 1 (Th1) in the CNS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.
The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (CNS), were examined to learn how they affect T cell differentiation in the CNS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-polymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional heterodimer, p70. In addition, the PDEI ibudilast also suppressed interferon-gamma, but not IL-4 or IL-10, production by myelin oligodendrocyte glycoprotein (MOG)-specific T cells reactivated with MOG in the presence of microglia. Thus, PDEIs may also suppress differentiation of T helper 1 (Th1) in the CNS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.
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