Role of liver X receptors alpha agonist on expressions of LPS-induced inflammatory response associated factor IRAK-4 and NF-kappaB in Kupffer cells

在 interleukin-1 受体的表情上探索激活的肝 X 受体(LXR ) 的角色的目的在在 Kupffer 房间并且到由 LPS 导致了的煽动性的反应联系了 kinase-4 (IRAK-4 ) 和 NF-kappaB (NF-B ) 调查煽动性的反应的 LXR 否定规定的可能的机制。Kupffer 房间被骨胶原灌注在 situ 从男 Kunming 老鼠孤立的方法。并且这些房间被划分成 4 个组：正常控制组， LPS 处理组， LXR 收缩筋 T0901317 处理组， LPS 和 T0901317 联合了处理组。 LPS 处理组在 RPMI 1640 与 1 g/ml LPS 的最后的集中被对待并且为 6 h 有教养， T0901317 处理组在 RPMI 1640 与 5 g/ml 的最后的集中被对待并且为 24 h 有教养，并且联合处理组在 RPMI 1640 与 1 g/ml T0901317 的最后的集中为 24 h 收到了文化前然后为有在 RPMI 1640 的 5 g/ml LPS 的最后的集中的 6 h 有教养。所有组为 30 h 是有教养的。在 mRNA 和蛋白质层次的 LXR， IRAK-4 和 NF-B 的表示被即时 PCR 并且西方的弄污检测，并且 TNF-1 和 IL-1 层次被 ELISA 检测。LXR mRNA 和蛋白质的层次是的结果在 LPS 组在 T0901317 组最高、最低(P < 0.05 ) 。IRAK4 和 NF-B mRNAs 和蛋白质的水平比在 LPS 组在联合对待的组是显然更低的(P < 0.05 ) 。并且 TNF-1 和 IL-1 的水平在 LPS 组最高被观察(P < 0.05 ) ，但是在控制组， T0901317 组和联合对待的组之中的没有差别(P > 0.05 ) 。这些标明日期的结论建议 LXR 收缩筋有效地装起来调整 LXR mRNA 和蛋白质的表情并且禁止煽动性的反应。这可能经由下面调整在 mRNA 和蛋白质层次的 IRAK4 和 NF-B 的表情。

Objective： To explore the role of activated liver X receptor α （LXRα） on the expressions of interleukin-1 receptor associated kinase-4 （IRAK-4） and NF-kappaB （NF-κB） in the inflammatory response which induced by LPS in the Kupffer cells and to investigate the possible mechanisms of LXRα negative regulation of inflammatory response. Methods： The Kupffer cells were isolated from male Kunming mice by collagen perfusion in situ. And these cells were divided into 4 groups： normal control group, LPS treatment group, LXRct agonist T0901317 treatment group, LPS and T0901317 combined treatment group. The LPS treatment group were treated with a final concentration of 1 μg/ml LPS in RPMI 1640 and cultured for 6 h, the T0901317 treatment group were treated with a final concentration of 5 μg/ml in RPMI 1640 and cultured for 24 h, and the combined treatment group received pre-culture for 24 h with a final concentration of 1μg/ml T0901317 in RPMI 1640 and then cultured for 6 h with a final concentration of 5 μg/ml LPS in RPMI 1640. All groups were cultured for 30 h. The expression of LXRα, IRAK-4 and NF-κB at mRNA and protein levels were detected by real-time PCR and Western blotting, and the TNF-α and IL-1β levels were detected by ELISA. Results： The levels of LXRα mRNA and protein were highest in T0901317 group, and lowest in LPS group （P〈0.05）. The level of IRAK4 and NF-κB mRNAs and proteins were evidently lower in the Combined-treated group than in LPS group （P〈0.05）. And the level of TNF-α and IL-1 were observed highest in LPS group （P〈0.05）, but no difference among the Control group, T0901317 group and Combined-treated group （P〉0.05）. Conclusion： These date suggest that the LXR agonists can effectively up-regulate the expressions of LXRα mRNA and protein and inhibit the inflammatory response. This may be via down-regulating the expressions of IRAK4 and NF-κB at mRNA and protein levels.