title: PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells.
abstract: 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 κB(NF-κB). 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 PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ 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-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB.
authors: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
authors: Keiko
authors: K
authors: Kan-o
authors: Koichiro
authors: K
authors: Matsumoto
authors: Yukari
authors: Y
authors: Asai-Tajiri
authors: Satoru
authors: S
authors: Fukuyama
authors: Saaka
authors: S
authors: Hamano
authors: Nanae
authors: N
authors: Seki
authors: Yoichi
authors: Y
authors: Nakanishi
authors: Hiromasa
authors: H
authors: Inoue
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis*; D002460:Cell Line; D004279:DNA, Viral / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D012330:RNA, Double-Stranded / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D004279:DNA, Viral; D012330:RNA, Double-Stranded