Sinomenine promotes differentiation but impedes maturation and co-stimulatory molecule expression of human monocyte-derived dendritic cells
Sinomenine promotes differentiation but impedes maturation and co-stimulatory molecule expression of human monocyte-derived dendritic cells
复制标题
青藤碱促进人单核细胞来源的树突状细胞分化但阻碍成熟和共刺激分子表达
DOI：
10.1016/j.intimp.2007.04.007
复制
发表时间：
2007-08-01
影响因子：
5.6
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
Chen, Yongwen;Yang, Chengying;Wu, Yuzhang
树突状细胞（DC）擅长将抗原呈递给T细胞，因此对诱导初次和二次免疫应答做出关键贡献。青藤碱具有免疫抑制和抗炎活性，几个世纪以来一直用于治疗自身免疫性疾病。然而，青藤碱对单核细胞来源的DC的分化、成熟和功能的影响尚未研究。我们在此表明，当在青藤碱（200 μ g/ml）存在下用GM-CSF和IL-4（IL-4）处理单核细胞时，DC分化被促进，如通过CD 1a的上调而CD 14降低所证明的。此外，未成熟DC与青藤碱孵育显著减弱脂多糖（LPS）诱导的DC成熟，如成熟标志物CD 83和共刺激分子（包括CD 86、B7-H1和CD 40）表达减少所示。此外，青藤碱也防止抗原（FITC-葡聚糖或荧光黄）的LPS处理的DC摄取减少。混合淋巴细胞反应（MLR）显示，青藤碱处理的DC阻碍共培养的CD 4（+）T细胞分泌细胞因子IL-2和IFN-γ。因此，青藤碱对DC分化、成熟和功能的调节与其在自身免疫性疾病、移植和其他免疫介导的病症中控制特异性免疫应答的免疫调节作用具有潜在相关性。(C)2007 Elsevier B. V.保留所有权利。
Dendritic cells (DC) excel at presenting antigen to T cells and thus make a key contribution to the induction of primary and secondary immune responses. Sinomenine has been used for centuries in the treatment of patients with autoimmune diseases as it possesses immumosuppressive and anti-inflammatory activities. However, the effect of sinomenine on the differentiation, maturation, and functionality of DC derived from monocytes has not been studied. We show here that DC differentiation is promoted when monocytes are treated with GM-CSF and IL-4 (IL-4) in the presence of sinomenine (200 mu g/ml), as evidenced by the upregulation of CD1a while CD14 was decreased. In addition, incubation of immature DC with sinomenine significantly blunted lipopolysaccharide (LPS)-induced DC maturation, as shown by the reduction of expression of the maturation marker CD83 and co-stimulatory molecules, including CD86, B7-H1, and CD40. Moreover, sinomenine also prevented decreases in antigen (FITC-Dextran or Lucifer Yellow) uptake by LPS-treated DC. Mixed lymphocyte reactions (MLRs) revealed that sinomenine-treated DC impede the secretion of the cytokines IL-2 and IFN-gamma by co-cultured CD4(+) T cells. Therefore, modulation of DC differentiation, maturation, and functionality by sinomenine is of potential relevance to its immunomodulatory effects in controlling specific immune responses in autoimmune diseases, transplantation, and other immune-mediated conditions. (C) 2007 Elsevier B.V. All rights reserved.