It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.

译文

已经确定氧化的LDL(ox-LDL)可以通过减少肿瘤坏死因子α(TNF-αm-RNA)来调节巨噬细胞的细胞因子分泌。但是,对氧化的高密度脂蛋白的作用知之甚少(ox-HDL)。这项研究报告了与ox-LDL和某些氧化产物(氢过氧化物和醛类)相比,ox-HDL亚组分2和3(ox-HDL2,ox-HDL3)对TNF分泌的影响THP-1人单核细胞衍生的α-α体外,将HDL2,HDL3和LDL用10 microM Cu氧化12 h和/或24 h,将天然和氧化的HDL和LDL与有或没有LPS的巨噬细胞一起孵育24 h (10 ng / ml),然后在培养基中测量TNF-α的分泌,脂质过氧化氢和非极性醛也与细胞一起孵育2小时,然后更换培养基,再过22 h后测量TNF-α的分泌ox-HDL2对TNF-α的抑制作用(p < .05),在存在和不存在LPS的情况下观察到THP-1巨噬细胞的ox-HDL3(p <.05)和ox-LDL(p <.05)。与ox-HDL孵育12小时和24小时后,这种抑制作用保持不变。亚油酸的氢过氧化物不会改变细胞的TNF-α分泌,而分析的八种醛中的五种(2,4-庚二烯醛,己醛,2-壬烯醛,2-辛烯醛,2,4-癸二烯醛)抑制TNF-α分泌(p <.05)。这些发现表明,ox-HDL及其某些脂质过氧化产物在巨噬细胞对炎症反应的调节中起着作用,正如以前对ox-LDL所观察到的一样。

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