Anti-inflammatory properties of cilostazol: Its interruption of DNA binding activity of NF-κB from the Toll-like receptor signaling pathways

International Immunopharmacology
Takuya SakamotoYuichi Hattori

Abstract

Cilostazol, a selective inhibitor of phosphodiesterase type III with anti-platelet, anti-mitogenic, and vasodilating properties, is widely used to treat ischemic symptoms of peripheral vascular disease. Ample evidence has suggested that cilostazol also exhibits an anti-inflammatory effect, but its anti-inflammatory mechanism is not fully understood. Here, we showed that cilostazol specifically inhibited expression of cytokines, which are induced by nuclear factor-κB (NF-κB) activation, in RAW264.7 macrophage cells stimulated with different Toll-like receptor (TLR) ligands. Cilostazol was found to significantly reduce TLR-4 and TLR-3 ligands-stimulated NF-κB transcriptional activity, which was quantified by luciferase reporter assays. However, cilostazol was without effect on IκBα degradation and NF-κB p65 phosphorylation and nuclear translocation after challenge with the TLR-4 ligand lipopolysaccharide (LPS). Cilostazol did not also prevent the LPS-induced increase in phosphorylated levels of the mitogen-activated protein kinase (MAPK) family. On the other hand, using chromatin immunoprecipitation assays, we demonstrated that cilostazol reduced the LPS-induced transcriptional activities of interleukin-6 and tumor necrosis facto...Continue Reading

Citations

Feb 5, 2019·Immunopharmacology and Immunotoxicology·Hae-Ri LeeTae-Hwe Heo
Aug 3, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Helmy MoawadMohammed A Alkhawlani
Aug 30, 2019·International Journal of Molecular Sciences·Kevin KojokYahye Merhi
Jan 9, 2021·International Immunopharmacology·Nadia Alice Vieira MottaFernanda Carla Ferreira de Brito
Jun 1, 2021·Immunopharmacology and Immunotoxicology·May Ahmed ShawkiRiham S Said
Aug 18, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Tokiko SuzukiYuichi Hattori

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