Cilostazol inhibits the expression of hnRNP A2/B1 and cytokines in human dermal microvascular endothelial cells

Abstract

Objectives: hnRNP A2/B1 has been identified as a target antigen of anti-endothelial cell IgA antibody in patients with Behçet's disease (BD). In addition, increased expression of cellular hnRNP A2/B1 is stimulated by Streptococcus sanguinis or the sera from patients with BD. We aimed to investigate the effects of cilostazol on the expression of hnRNP A2/B1 and chemokines in human dermal microvascular endothelial cells (HDMECs).

Methods: Expression of hnRNP A2/B1, cytokines, and chemokines in HDMECs was induced by tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and lipopolysaccharide (LPS). HDMECs were treated with cilostazol (10 μM) and the inhibitory effects were evaluated with real-time polymerase chain reaction and immunocytochemistry.

Results: Expression of hnRNP A2/B1, CXCL1, CXCL2, CXCL8, and IL-1β mRNA was significantly increased in HDMECs treated with all three stimulants. In addition, mRNA expression of hnRNP A2/B1 and inflammatory mediators was significantly inhibited in HDMECs treated with various stimulants with cilostazol pretreatment. Immunocytochemistry demonstrated that cilostazol pretreatment effectively inhibited the stimulant-induced increased expression of hnRNP A2/B1 in the nucleus and cytoplasm of HDMECs.

Conclusions: Cilostazol pretreatment can reduce the excessive expression of inflammatory cytokines and chemokines and hnRNP A2/B1 by the BD-related stimulants, including TNF-α, IL-1β, and LPS, in HDMECs. We suggest that cilostazol may have therapeutic efficacy in inhibiting the major inflammatory reaction in the pathogenesis of BD.