Proteinase-Activated Receptor-2–Triggered Prostaglandin E2 Release, but Not Cyclooxygenase-2 Upregulation, Requires Activation of the Phosphatidylinositol 3–Kinase / Akt / Nuclear Factor-κB Pathway in Human Alveolar Epithelial Cells
スポンサーリンク
概要
- 論文の詳細を見る
Proteinase-activated receptor-2 (PAR2) triggers upregulation of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) formation in human alveolar epithelial A549 cells. This COX-2 upregulation appears to involve the Src / epidermal growth factor (EGF) receptor / p38 MAP kinase (p38MAPK) pathway and also the cAMP-response element–binding protein (CREB) pathway. Here, we investigated the roles of nuclear factor-κB (NF-κB)–related signals in the PAR2-triggered PGE2 release / COX-2 upregulation in A549 cells. The PAR2-triggered PGE2 release was clearly blocked by an inhibitor of the NF-κB pathway. Stimulation of PAR2 actually caused phosphorylation of inhibitor-κB, an indicator of NF-κB activation, an effect being blocked by inhibitors of MEK, phosphatidylinositol 3–kinase (PI3-kinase), and Akt, but little or not by inhibitors of p38MAPK and JNK. Stimulation of PAR2 also caused phosphorylation of Akt, an effect suppressed by inhibitors of PI3-kinase and MEK. Nonetheless, the PAR2-triggered upregulation of COX-2 was resistant to inhibitors of NF-κB, PI3-kinase, and Akt, but was attenuated by inhibitors of MEK and JNK. Stimulation of PAR2 induced phosphorylation of CREB, an effect abolished by an inhibitor of MEK but not inhibitors of p38MAPK EGF receptor. These findings demonstrate that the MEK / ERK / PI3-kinase / Akt / NF-κB pathway is involved in PAR2-triggered PGE2 formation, but not upregulation of COX-2 that is dependent on activation of ERK/CREB and JNK in addition to p38MAPK.
論文 | ランダム
- Distributed Throughput-Based Fair Queueing for Wired and Wireless Packet Communication Networks(QoS, 無線ネットワーク,アドホックネットワーク,センサネットワーク及び一般)
- 次世代移動通信システムにおける所要周波数帯域幅算出法(国際標準に向けたテレコム技術とその効用論文)
- 次世代無線通信システムにおけるパケット交換トラヒックの容量計算 : 無線チャネル上の送信に対する集団到着M/G/1非割込優先処理待ち行列モデル(トラヒック, 一般)
- 次世代無線通信システムにおけるパケット交換トラヒックの容量計算 : 無線チャネル上の送信に対する集団到着M/G/1非割込優先処理待ち行列モデル
- Lisuride[N-(D-6-Methy-8-isoergolinyl)-N',N'-diethyl-Urea hydrogenmaleate]の女性内分泌機能に及ぼす影響