Immunopathology Lab, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore 632 014, Tamil Nadu, India.
Immunopathology Lab, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore 632 014, Tamil Nadu, India.
Int Immunopharmacol. 2018 Aug;61:64-73. doi: 10.1016/j.intimp.2018.05.019. Epub 2018 May 26.
In the present study, we intend to gain an insight into the mechanism of Withaferin-A (WA), a steroidal lactone with reference to repolarization of RAW 264.7 macrophages (M1 to M2 type). We found that successful internalization of WA via mannosylated liposomal delivery system (ML-WA) reduced the RAW 264.7 macrophage (M1) mediated pro-inflammatory cytokines (IL-1β, IL-6, IL-23, and TNF-α) through the attenuation of transcription factor NF-κB-p65 expression. Whereas, ML-WA treatment induced a controlled upregulation of p-STAT3, and ablated the key oxidative stress markers (NO, iNOS, and ROS) in M1 → M2 RAW 264.7 macrophage repolarization, which suggested the recalibration of M1 macrophage metabolic function. Further, the elevated expression of M2 macrophage associated CD163 over the M1 macrophage related CD86 concluded that ML-WA induces an anti-inflammatory response by repolarizing the M1 → M2 RAW 264.7 macrophage.
在本研究中，我们旨在深入了解 Withaferin-A（WA）的作用机制，这是一种甾体内酯，与 RAW 264.7 巨噬细胞（M1 向 M2 型）的复极化有关。我们发现，通过甘露糖化脂质体递送系统（ML-WA）成功内化 WA 可以通过减弱转录因子 NF-κB-p65 的表达来减少 RAW 264.7 巨噬细胞（M1）介导的促炎细胞因子（IL-1β、IL-6、IL-23 和 TNF-α）。然而，ML-WA 处理诱导了 p-STAT3 的受控上调，并消除了 M1→M2 RAW 264.7 巨噬细胞重极化中的关键氧化应激标志物（NO、iNOS 和 ROS），这表明 M1 巨噬细胞代谢功能的重新校准。此外，M2 巨噬细胞相关的 CD163 的表达升高超过了 M1 巨噬细胞相关的 CD86，这表明 ML-WA 通过使 M1→M2 RAW 264.7 巨噬细胞复极化来诱导抗炎反应。
