The persistent activation of intestinal mechanistic target of rapamycin complex 1 (mTORC1) triggered by mucosal stress has been linked to deregulation of the gut immune response resulting in intestinal inflammation and cell death. The present study investigated the regulatory properties of food-derived mTORC1 modulators, curcumin, and piperine, toward the polarization of stimulated macrophages and the differentiation of monocytes at two mTORC1 activity levels (baseline and elevated). To that end, we created stable human THP-1 monocytes exhibiting normal or constitutively active mTORC1. Curcumin or its combination with piperine, but not piperine alone, suppressed mTORC1 kinase activity, curtailed lipopolysaccharide-mediated inflammatory response of THP-1 macrophages, and repressed macrophage activation by inhibiting signaling pathways involved in M1 (mTORC1) and M2 (mTORC2 and cAMP response element binding protein) polarization. The effects of piperine in the curcumin/piperine combination were modest overall, indicating it was curcumin that modulated differentiating monocytes into acquiring a M0 macrophage phenotype characterized by low inflammatory cytokine output.

由粘膜应激触发的雷帕霉素复合物 1 (mTORC1) 肠道机制靶标的持续激活与肠道免疫反应的失调导致肠道炎症和细胞死亡有关。本研究调查了食物来源的 mTORC1 调节剂、姜黄素和胡椒碱在两个 mTORC1 活性水平（基线和升高）下对刺激巨噬细胞极化和单核细胞分化的调节特性。为此，我们创造了稳定的人类 THP-1 单核细胞，表现出正常或组成性活性的 mTORC1。姜黄素或其与胡椒碱的组合，但不是单独的胡椒碱，抑制 mTORC1 激酶活性，减少脂多糖介导的 THP-1 巨噬细胞炎症反应，通过抑制参与 M1 (mTORC1) 和 M2 (mTORC2 和 cAMP 反应元件结合蛋白) 极化的信号通路来抑制巨噬细胞活化。胡椒碱在姜黄素/胡椒碱组合中的作用总体上不大，表明姜黄素调节分化的单核细胞获得以低炎症细胞因子输出为特征的 M0 巨噬细胞表型。