7α-hydroxy Cholesterol is an endogenous oxidized cholesterol metabolite. 7α-hydroxy Cholesterol serves as a key rate-limiting intermediate in the bile acid biosynthesis pathway and a potential biomarker for lipid peroxidation. 7α-hydroxy Cholesterol can be used in research related to cardiovascular metabolic diseases such as atherosclerosis, as well as long-acting anti-tumor immunotherapy using TCR-T cells[1-4].
In vitro, 7α-hydroxy Cholesterol (5μg/ml) was applied to treat THP-1 monocytes for 6-48 hours. 7α-hydroxy Cholesterol significantly upregulated the expression of pattern recognition receptors (TLR6 and CD14) and chemokines (CCL2, CCL3, and CCL4). 7α-hydroxy Cholesterol enhanced cellular immune responses to PAMPs (such as FSL-1 and LPS) and immune cell migration, while simultaneously activating the phosphorylation of the Akt, Src, ERK1/2, and NF-κB signaling pathways[5]. 7α-hydroxy Cholesterol (12.5-100ng/ml) was used to treat HeLa cells for 24 hours, followed by stimulation with pyolysin for 2 hours. 7α-hydroxy Cholesterol significantly inhibited lactate dehydrogenase (LDH) leakage and cytolysis. 7α-hydroxy Cholesterol prevented the activation of MAPK cell stress responses and limited alterations in the cytoskeleton[6].
References:
[1] Cho HR, Son Y, Kim SM, et al. 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor. PLoS One. 2017 Mar 21;12(3):e0173749.
[2] Crosignani A, Zuin M, Allocca M, et al. Oxysterols in bile acid metabolism. Clin Chim Acta. 2011 Nov 20;412(23-24):2037-45.
[3] Kim BY, Son Y, Kim BJ, et al. Atheroma-Relevant 7-Oxysterols Differentially Upregulate Cd14 Expression. Int J Mol Sci. 2023 Jun 23;24(13):10542.
[4] Nury T, Samadi M, Zarrouk A, et al. Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4α- and 4β-hydroxycholesterol) and C7 (7-ketocholesterol, 7α- and 7β-hydroxycholesterol) on cells of the central nervous system. Eur J Med Chem. 2013;70:558-67.
[5] Son Y, Kim BY, Kim M, et al. Glucocorticoids Impair the 7α-Hydroxycholesterol-Enhanced Innate Immune Response. Immune Netw. 2023 Oct 19;23(5):e40.
[6] Ormsby TJR, Owens SE, Clement L, et al. Oxysterols Protect Epithelial Cells Against Pore-Forming Toxins. Front Immunol. 2022 Jan 26;13:815775.
7α-hydroxy Cholesterol是一种内源性的氧化胆固醇代谢物。7α-hydroxy Cholesterol是胆汁酸生物合成途径中的关键限速中间体及脂质过氧化的潜在生物标志物。7α-hydroxy Cholesterol可用于动脉粥样硬化等心血管代谢疾病以及TCR-T细胞长效抗肿瘤免疫治疗的相关研究[1-4]。
在体外，7α-hydroxy Cholesterol（5μg/ml）处理THP-1单核细胞6-48小时。7α-hydroxy Cholesterol显著上调了模式识别受体（TLR6和CD14）及趋化因子（CCL2、CCL3和CCL4）的表达。7α-hydroxy Cholesterol增强了细胞对PAMPs（如FSL-1和LPS）的免疫应答及免疫细胞迁移，同时激活了Akt、Src、ERK1/2和NF-κB信号通路的磷酸化[5]。7α-hydroxy Cholesterol（12.5-100ng/ml）处理HeLa细胞24小时，随后以pyolysin刺激2h。7α-hydroxy Cholesterol显著抑制乳酸脱氢酶（LDH）的泄漏及细胞溶解，防止MAPK细胞应激反应的激活并限制细胞骨架的改变[6]。