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
- 画像処理による電子部品装着機の部品位置計測手法
- 活動的な火口湖中の硫酸の硫黄および酸素同位体比からみたマグマ-熱水系 (総特集 地殻化学のフロンティア--脇田宏教授退官記念号) -- (2章 火山と化学)
- ニオス湖におけるマグマ性CO2の蓄積 (総特集 新しい地球化学の構築--酒井均教授退官記念号) -- (5章 同位体地球化学)
- 326. 高解像度 X 線 TV 断層システム (第 2 報)(第 46 回総会学術大会会員研究発表予稿)
- 320 X線TV断層撮影による肺野病変の描出能