Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 8, Issue 10, Pages 1408-1417Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2008.05.012
Keywords
Th17; PDE4; autoimmune diseases; memory T cells
Categories
Funding
- National Key Basic Research Program of China [2007CB512404]
- Research Groups Fund of Guangdong Province Natural Science [05200176]
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Th17 cells are highly proinflammatory and involved in the immunopathogenesis of severe autoimmune diseases. Selective phosphodiesterase 4 (PDE4) inhibitors, which elevate intracellular cAMP by inhibiting the hydrolysis of cAMP, have been demonstrated to be an effective anti-inflammatory agent in airway inflammatory diseases. In the present study, we assessed the effect of a selective PDE4 inhibitor Zl-n-91 on IL-17 production by PBMCs and by purified CD4(+) T cells following stimulation. The results for the first time demonstrated that the addition of Zl-n-91 into cell cultures of PBMCs and purified CD4(+) T cells could result in the suppression of IL-17 production at the protein and mRNA levels. Further analysis indicated that Zl-n-91 had a direct inhibitory effect on the IL-17 production by memory Th17 cells via the suppression of activation, proliferation and division of CD4(+) T cells. Our data suggested that Zl-n-91 might have beneficial effects in the treatment of IL-17-related autoimmune diseases. (c) 2008 Elsevier B.V. All rights reserved.
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