School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology, South Korea.
World J Gastroenterol. 2011 Feb 28;17(8):976-86. doi: 10.3748/wjg.v17.i8.976.
To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.
Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7), mouse primary antigen-presenting cells (APCs, MHCII(+)) and CD11c(+) dendritic cells to analyze the effects of cinnamon extract on APC function. The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production, and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry. In addition, the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H(3)]-thymidine incorporation and cytokine analysis, respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo, cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid. The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms, histological analysis and cytokine expression profiles in inflamed tissue.
Treatment with cinnamon extract inhibited maturation of MHCII(+) APCs or CD11c(+) dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1, B7.2, ICOS-L), MHCII and cyclooxygenase (COX)-2. Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4(+) T cells into IL-10(high) CD4(+) T cells. Furthermore, oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines (IL-1β, IFN-γ and TNF-α), while enhancing IL-10 levels.
Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10(+) regulatory T cells.
研究肉桂提取物的抗炎作用，并阐明其针对抗原呈递细胞功能的作用机制。
用肉桂提取物处理鼠巨噬细胞系（Raw 264.7）、小鼠原代抗原呈递细胞（MHCII(+)）和 CD11c(+)树突状细胞，分析肉桂提取物对 APC 功能的影响。通过定量实时 PCR 和流式细胞术分析细胞因子产生以及 MHC 抗原和共刺激分子的表达，研究肉桂提取物对 APC 的作用机制。此外，通过[H(3)]-胸苷掺入和细胞因子分析分别分析肉桂提取物对抗原呈递能力和 APC 依赖性 T 细胞分化的影响。为了证实肉桂提取物在体内的抗炎作用，用肉桂或 PBS 对小鼠进行 20 天的口服处理，然后用 2,4,6-三硝基苯磺酸诱导实验性结肠炎。通过检查临床症状、组织学分析和炎症组织中细胞因子表达谱来测量肉桂提取物对实验性结肠炎的保护作用。
肉桂提取物通过抑制共刺激分子（B7.1、B7.2、ICOS-L）、MHCII 和环氧化酶（COX）-2 的表达来抑制 MHCII(+)APC 或 CD11c(+)树突状细胞（DC）的成熟。肉桂提取物诱导产生低水平促炎细胞因子（IL-1β、IL-6、IL-12、IFN-γ 和 TNF-α）而高表达免疫调节细胞因子（IL-10 和转化生长因子-β）的调节性 DC（rDC）。此外，肉桂提取物产生的 rDC 抑制 APC 依赖性 T 细胞增殖，并将 CD4(+)T 细胞转化为 IL-10(high)CD4(+)T 细胞。此外，肉桂提取物的口服给药通过抑制 COX-2 和促炎细胞因子（IL-1β、IFN-γ 和 TNF-α）的表达，同时提高 IL-10 水平，抑制肠道结肠炎的发展和进展。
我们的研究表明，肉桂提取物作为一种抗炎剂具有潜力，它通过靶向调节性 APC 和 IL-10(+)调节性 T 细胞的生成来发挥作用。
