SUMMARY
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-alpha) 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-kappaB) activation. Our results indicated that cilostazol treatment decreased IkappaBalpha
degradation and inhibited NF-kappaB p65 translocation, and the inhibitory effects of cilostazol were cAMP-independent. Therefore, inhibition of
NF-kappaB 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.
KEY WORDS
atherosclerosis; cilostazol; dendritic cells; lipopolysaccharide; nuclear factor-kappa B
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