Biochem J. 2014 Apr 15;459(2):e1-3. doi: 10.1042/BJ20140211.
Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Accumulation of cholesterol and its intermediates, such as oxysterols, lead to activation of the nuclear receptors LXRs (liver X receptors). LXR is an important regulator of cholesterol homoeostasis by controlling its transport and its neo-synthesis. Accumulating evidence indicates that the endogenous ligands of LXRs, oxysterols, play an active and important role in regulating the fate and function of immune cells. Indeed, LXRs are negative regu-lators of innate immunity by interfering with macrophage activation. Recent advances have highlighted a controversial role for LXR in cancer. In this issue of the Biochemical Journal, Wang et al. propose that LXR agonist directly controls IFN-γ (interferon-γ) expression, which limits tumour growth. This protective effect mediated by LXR appears to be dependent on IFN-γ. Thus, despite accumulation of endogenous ligand of LXR in cancer, activation of LXR seems protective. This novel evidence provides a new perspective for targeting LXR in cancer, although controversial studies can be also found in the literature. In order to avoid side effects associated with LXR agonists, molecular and cellular studies are required to decipher this unexpected action of LXRs.
胆固醇在调节哺乳动物细胞膜特性方面起着不可或缺的作用。胆固醇及其中间产物（如氧化固醇）的积累会导致核受体 LXR（肝 X 受体）的激活。LXR 是通过控制胆固醇的运输和新合成来调节胆固醇稳态的重要调节剂。越来越多的证据表明，LXR 的内源性配体氧化固醇在调节免疫细胞的命运和功能方面发挥着积极而重要的作用。事实上，LXR 通过干扰巨噬细胞的激活来负调控先天免疫。最近的进展强调了 LXR 在癌症中的争议作用。在本期《生物化学杂志》中，Wang 等人提出 LXR 激动剂直接控制 IFN-γ（干扰素-γ）的表达，从而限制肿瘤生长。这种由 LXR 介导的保护作用似乎依赖于 IFN-γ。因此，尽管癌症中 LXR 的内源性配体积累，但 LXR 的激活似乎具有保护作用。尽管文献中也有争议性的研究，但这一新证据为癌症中靶向 LXR 提供了新的视角。为了避免与 LXR 激动剂相关的副作用，需要进行分子和细胞研究来破译 LXR 的这种意外作用。
