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首页> 外文期刊>Biomolecules & therapeutics >7 alpha-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells
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7 alpha-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells

机译：7α-羟基胆固醇引起TLR6介导的IL-23在单核细胞中的表达

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摘要

We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. 7 alpha-Hydroxycholesterol (7 alpha OHChol) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with 7 alpha OHChol resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit alpha (p19) and the IL-12 subunit beta (p40). However, treatment with 7-ketocholesterol (7K) and 7 beta-hydroxycholesterol (7 beta OHChol) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or 7 beta OHChol did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by 7 alpha OHChol as well as secretion of IL-23 enhanced by 7 alpha OHChol plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like 7 alpha OHChol can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.
机译：我们通过检查7氧化胆固醇衍生物对单核细胞中IL-23表达的影响，研究了7氧化胆固醇衍生物是否会影响动脉粥样硬化的炎症和/或免疫反应。 7α-羟基胆固醇（7αOHChol）诱导TLR6基因的转录并提高THP-1单核细胞中细胞表面TLR6蛋白的水平。通过用7 alpha OHChol处理将TLR6 FSL-1激动剂添加到表达TLR6的细胞中，会导致IL-23的产生增强以及编码IL-23亚基α（p19）和IL-12亚基的基因转录beta（p40）。但是，用7-酮胆固醇（7K）和7β-羟基胆固醇（7 beta OHChol）处理不会影响TLR6的表达，并且在用7K或7 beta OHChol处理的细胞中添加FSL-1不会影响基因的转录。 ERK，Akt或PI3K的药理抑制作用导致7αOHChol诱导的TLR6转录减弱，以及7αOHChol加FSL-1增强的IL-23分泌。 p38 MAPK或JNK的抑制导致IL-23分泌减少。这些结果表明，某种类型的7-氧化胆固醇（如7αOHChol）可以通过PI3K / Akt和MAPKs途径引发单核细胞的TLR6介导的IL-23表达。

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