Cilostazol is a phosphodiesterase-3 inhibitor that functions as a platelet aggregation inhibitor and is used for treating peripheral artery diseases and ischemic stroke. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. Cilostazol has anti-atherogenic and anti-inflammatory effects, but the effects of cilostazol on DC maturation remain unknown. The purpose of this study was to determine the effects of cilostazol on lipopolysaccharide (LPS)-induced maturation of DCs. DC2.4 cells were treated with cilostazol for 12 h and subsequently stimulated with LPS to induce maturation. Cilostazol reduced the expression of maturation-associated markers induced by LPS, such as CD40, CD86, and MHCII, improved the endocytotic function, and decreased production of the tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) of these cells. To further elucidate the mechanisms responsible for the inhibition of DC2.4 maturation by cilostazol, we investigated the effect of cilostazol on LPS-stimulated nuclear factor-kappa B (NF-κB) activation. Our results indicated that cilostazol treatment decreased IκBα degradation and inhibited NF-κB p65 translocation, and the inhibitory effects of cilostazol were cAMP-independent. Therefore, inhibition of NF-κB by cilostazol might result in the suppression of DC maturation. In conclusion, cilostazol suppressed LPS-stimulated DC maturation, which might contribute to its anti-atherosclerosis effect.
- MeSH
- antigeny CD40 imunologie MeSH
- antigeny CD86 imunologie MeSH
- ateroskleróza imunologie patofyziologie MeSH
- buněčná imunita imunologie účinky léků MeSH
- dendritické buňky * chemie imunologie účinky léků MeSH
- fibrinolytika MeSH
- histokompatibilita - antigeny třídy II imunologie MeSH
- inhibitory agregace trombocytů MeSH
- inhibitory fosfodiesterasy 3 MeSH
- interleukin-6 imunologie MeSH
- lipopolysacharidy terapeutické užití MeSH
- NF-kappa B * genetika imunologie účinky léků MeSH
- polymerázová řetězová reakce MeSH
- průtoková cytometrie MeSH
- techniky in vitro MeSH
- tetrazoly * farmakologie imunologie MeSH
- TNF-alfa imunologie MeSH
- vazodilatancia MeSH
- western blotting MeSH
- Publikační typ
- práce podpořená grantem MeSH
