화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.435, No.2, 195-201, 2013
PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells
Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor kappa B(NF-kappa B). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3K delta in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110 delta was detected by Western blot and suppressed by pretreatment with PI3K delta siRNA. The activation of PI3K delta is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-kappa B was suppressed by a pan-PI3K inhibitor but not by a PI3K delta inhibitor. These results suggest that PI3K delta mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-kappa B. (c) 2013 Elsevier Inc. All rights reserved.