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姜黄素抑制树突状细胞的免疫刺激功能:丝裂原活化蛋白激酶和核因子κB的易位作为潜在靶点。

Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets.

作者信息

Kim Gi-Young, Kim Ki-Hyung, Lee Soong-Hwan, Yoon Man-Soo, Lee Hee-Jeong, Moon Dong-Oh, Lee Chang-Min, Ahn Soon-Cheol, Park Young Chul, Park Yeong-Min

机构信息

Department of Microbiology and Immunology, and National Research Lab of Dendritic Cell Differentiation & Regulation and Medical Research Institute, Pusan National University College of Medicine, Pusan, South Korea.

出版信息

J Immunol. 2005 Jun 15;174(12):8116-24. doi: 10.4049/jimmunol.174.12.8116.

Abstract

Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and anticarcinogenic activities. However, the effect of curcumin on the maturation and immunostimulatory function of dendritic cells (DC) largely remains unknown. In this study, we examined whether curcumin can influence surface molecule expression, cytokine production, and their underlying signaling pathways in murine bone marrow-derived DC. DC were derived from murine bone marrow cells and used as immature or LPS-stimulated mature cells. The DC were tested for surface molecule expression, cytokine production, dextran uptake, the capacity to induce T cell differentiation, and their underlying signaling pathways. Curcumin significantly suppressed CD80, CD86, and MHC class II expression, but not MHC class I expression, in the DC. The DC also exhibited impaired IL-12 expression and proinflammatory cytokine production (IL-1beta, IL-6, and TNF-alpha). The curcumin-treated DC were highly efficient at Ag capture, via mannose receptor-mediated endocytosis. Curcumin inhibited LPS-induced MAPK activation and the translocation of NF-kappaB p65. In addition, the curcumin-treated DC showed an impaired induction of Th1 responses and a normal cell-mediated immune response. These novel findings provide new insight into the immunopharmacological role of curcumin in impacting on the DC. These novel findings open perspectives for the understanding of the immunopharmacological role of curcumin and therapeutic adjuvants for DC-related acute and chronic diseases.

摘要

姜黄素已被证明具有抗炎、抗诱变和抗癌活性。然而,姜黄素对树突状细胞(DC)成熟和免疫刺激功能的影响在很大程度上仍不清楚。在本研究中,我们检测了姜黄素是否能影响小鼠骨髓来源DC的表面分子表达、细胞因子产生及其潜在的信号通路。DC来源于小鼠骨髓细胞,用作未成熟或LPS刺激的成熟细胞。对DC进行表面分子表达、细胞因子产生、葡聚糖摄取、诱导T细胞分化的能力及其潜在信号通路的检测。姜黄素显著抑制DC中CD80、CD86和MHC II类分子的表达,但不影响MHC I类分子的表达。DC还表现出IL-12表达受损和促炎细胞因子产生(IL-1β、IL-6和TNF-α)减少。经姜黄素处理的DC通过甘露糖受体介导的内吞作用高效摄取抗原。姜黄素抑制LPS诱导的MAPK激活和NF-κB p65的转位。此外,经姜黄素处理的DC诱导Th1反应的能力受损,但细胞介导的免疫反应正常。这些新发现为姜黄素在影响DC方面的免疫药理学作用提供了新的见解。这些新发现为理解姜黄素的免疫药理学作用以及DC相关急慢性疾病的治疗佐剂开辟了前景。

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