A selective phosphodiesterase 4 (PDE4) inhibitor Zl-n-91 suppresses IL-17 production by human memory Th17 cells.
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.
Ma
Ruihong
R
Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Key Laboratory of Tropical Diseases Control, Guangzhou 510080, PR China.
Yang
Bin-Yan
BY
Wu
Chang-You
CY
D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D020889:Rolipram / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism
D020381:Interleukin-17; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D020889:Rolipram