The Inhibitory Effect of PIK-75 on Inflammatory Mediator Response Induced by Hydrogen Peroxide in Feline Esophageal Epithelial Cells
The Inhibitory Effect of PIK-75 on Inflammatory Mediator Response Induced by Hydrogen Peroxide in Feline Esophageal Epithelial Cells
复制标题
PIK-75对过氧化氢诱导的猫食管上皮细胞炎症介质反应的抑制作用
作者：
J. Jeong;Y. Lee;Jeong Hoon Han;Sun Young Park;K. Hwang;U. Sohn
磷酸肌醇3-激酶（PI 3 K）激活的亚型选择性抑制剂通过减少促炎细胞因子而具有抗炎作用。用过氧化氢和PIK-75处理第3~4代培养的猫食管上皮细胞（EEC）。MTT掺入法测定细胞活力。从蛋白质印迹推断PI 3 K亚型、p-Akt、IL-1β和IL-8的分布。ELISA法测定IL-6的释放。如果用PIK-75预处理细胞并用300 μM过氧化氢处理，则细胞形态与未处理细胞无显著差异。H_2O_2处理后，PI 3 K的p110α表达增加，而其它类型的p110α表达无明显变化。当细胞暴露于PIK-75和过氧化氢时，p-Akt的密度比单独的过氧化氢处理更呈剂量依赖性地降低。p-Akt的减少表明PIK-75对PI 3 K的抑制。与仅过氧化氢处理相比，PIK-75剂量依赖性地降低IL-1β、IL-8的表达和IL-6的水平。这些结果表明，p110α介导食管炎症，PIK-75通过减少猫食管上皮培养细胞上的促炎细胞因子而具有抗炎作用。
Isoform-selective inhibitors of phosphoinositide 3-kinase (PI3K) activation have an anti-inflammatory effect by reducing proinflammatory cytokines. Cultured feline esophageal epithelial cells (EEC) of passages 3~4 were treated with hydrogen peroxide and PIK-75. The cell viability was measured by a MTT incorporation assay. The distribution of PI3K isoforms, p-Akt, IL-1β, and IL-8 was inferred from Western blots. The release of IL-6 was determined by ELISA. The cell morphology was not considerably different from nontreated cells if the cells were pretreated with PIK-75 and treated with 300 μM hydrogen peroxide. The density of p110α of PI3K was increased, but that of other types was not affected after the treatment with hydrogen peroxide. The density of p-Akt, when the cells were exposed to PIK-75 and hydrogen peroxide, was diminished dose dependently more than that of hydrogen peroxide treatment only. The decrease of p-Akt showed an inhibition of PI3K by PIK-75. PIK-75 dose dependently reduced the expression of IL-1β, IL-8, and the level of IL-6 compared with hydrogen peroxide treatment only. These results suggest evidence that p110α mediates esophageal inflammation and that PIK-75 has an anti-inflammatory effect by reducing proinflammatory cytokines on feline esophageal epithelial cultured cells.
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DOI：
10.1152/ajpgi.00216.2004
发表时间：
2004-12-01
影响因子：
4.5
作者：
Cao, WB;Cheng, L;Harnett, KM
通讯作者：
Harnett, KM
影响因子：
--
作者：
Toker, Alex;Marmiroli, Sandra
通讯作者：
Marmiroli, Sandra
影响因子：
2.5
作者：
Jagannath Pal;M. Fulciniti;P. Nanjappa;Leutz Buon;Y. Tai;P. Tassone;N. Munshi;M. Shammas
通讯作者：
Jagannath Pal;M. Fulciniti;P. Nanjappa;Leutz Buon;Y. Tai;P. Tassone;N. Munshi;M. Shammas
影响因子：
--
作者：
Li, Jing;Song, Jun;Evers, B. Mark
通讯作者：
Evers, B. Mark
影响因子：
45.3
作者：
Janku, Filip;Wheler, Jennifer J.;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle