Han S J, Choi J H, Ko H M, Yang H W, Choi I W, Lee H K, Lee O H, Im S Y
Department of Microbiology, College of Natural Sciences, Chonnam National University, HRC, Kwangju, Republic of Korea.
Eur J Immunol. 1999 Apr;29(4):1334-41. doi: 10.1002/(SICI)1521-4141(199904)29:04<1334::AID-IMMU1334>3.0.CO;2-0.
Lipopolysaccharide (LPS) is a known inducer of numerous pro-inflammatory events including the production of platelet-activating factor (PAF). PAF released in response to LPS is a major contributor to the pathological events associated with endotoxemia. The present study demonstrates that dexmethasone (DEX) inhibited the LPS-induced early plasma PAF raise in a dose- and time-dependent manner. In addition, DEX prevented the subsequent PAF-mediated pathological phenomena such as anaphylactic shock-like symptoms, symptoms of disseminated intravascular coagulation and hemorrhage in renal medullae. DEX or the PAF antagonist BN 50739 significantly inhibited LPS-induced NF-kappaB activation. The inhibition of NF-kappaB activation by DEX was overcome by the injection of exogenous PAF. Administration of PAF or LPS resulted in a rapid loss of IkappaBalpha protein. The LPS-induced degradation of IkappaBalpha was prevented by pretreatment with BN 50739, suggesting that PAF is a critical intermediate in the LPS-triggered degradation of IkappaBalpha protein. DEX prevented the LPS-induced IkappaBalpha degradation, which was also reversed by exogenous PAF. Administration of DEX or BN 50739 caused an increase in cytoplasmic IkappaBalpha level. Our results indicate that DEX inhibits IkappaBalpha degradation and subsequent NF-kappaB activation through blocking the initial release of PAF.
脂多糖（LPS）是多种促炎事件的已知诱导剂，包括血小板活化因子（PAF）的产生。响应LPS释放的PAF是与内毒素血症相关的病理事件的主要促成因素。本研究表明，地塞米松（DEX）以剂量和时间依赖性方式抑制LPS诱导的早期血浆PAF升高。此外，DEX预防了随后PAF介导的病理现象，如过敏性休克样症状、弥散性血管内凝血症状和肾髓质出血。DEX或PAF拮抗剂BN 50739显著抑制LPS诱导的NF-κB活化。注射外源性PAF可克服DEX对NF-κB活化的抑制作用。给予PAF或LPS会导致IκBα蛋白迅速丢失。用BN 50739预处理可防止LPS诱导的IκBα降解，表明PAF是LPS触发的IκBα蛋白降解的关键中间体。DEX可防止LPS诱导的IκBα降解，外源性PAF也可逆转这种降解。给予DEX或BN 50739会导致细胞质IκBα水平升高。我们的结果表明，DEX通过阻断PAF的初始释放来抑制IκBα降解和随后的NF-κB活化。
