Glucocorticoids prevent NF-κB activation by inhibiting the early release of platelet-activating factor in response to lipopolysaccharide
✍ Scribed by Su Ji Han; Jung Hwa Choi; Hyun Mi Ko; Hae Won Yang; Il Whan Choi; Hern Ku Lee; Oh Hyoung Lee; Suhn-Young Im
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 120 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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-O B activation. The inhibition of NF-O B activation by DEX was overcome by the injection of exogenous PAF. Administration of PAF or LPS resulted in a rapid loss of I O B § protein. The LPS-induced degradation of I O B § was prevented by pretreatment with BN 50739, suggesting that PAF is a critical intermediate in the LPS-triggered degradation of I O B § protein. DEX prevented the LPS-induced I O B § degradation, which was also reversed by exogenous PAF. Administration of DEX or BN 50739 caused an increase in cytoplasmic I O B § level. Our results indicate that DEX inhibits I O B § degradation and subsequent NF-O B activation through blocking the initial release of PAF.