Chen Yongwen, Yang Chengying, Jin Naishi, Xie Zhunyi, Fei Lie, Jia Zhengcai, Wu Yuzhang
Laboratory of Immunoregulation, Institute of Immunology, PLA, The Third Military Medical University, Chongqing, 400038, PR China.
Int Immunopharmacol. 2007 Aug;7(8):1102-10. doi: 10.1016/j.intimp.2007.04.007. Epub 2007 May 2.
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 immunosuppressive 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 microg/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.
树突状细胞（DC）在将抗原呈递给T细胞方面表现出色，因此对原发性和继发性免疫反应的诱导起着关键作用。青藤碱因其具有免疫抑制和抗炎活性，已被用于治疗自身免疫性疾病患者数百年。然而，青藤碱对源自单核细胞的DC的分化、成熟和功能的影响尚未得到研究。我们在此表明，当单核细胞在青藤碱（200微克/毫升）存在的情况下用GM-CSF和IL-4（IL-4）处理时，DC分化得到促进，这通过CD1a的上调而CD14的降低得以证明。此外，用青藤碱孵育未成熟DC可显著抑制脂多糖（LPS）诱导的DC成熟，这表现为成熟标志物CD83以及共刺激分子（包括CD86、B7-H1和CD40）表达的降低。此外，青藤碱还可防止LPS处理的DC对抗原（FITC-葡聚糖或路西法黄）摄取的减少。混合淋巴细胞反应（MLR）显示，经青藤碱处理的DC会阻碍共培养的CD4(+) T细胞分泌细胞因子IL-2和IFN-γ。因此，青藤碱对DC分化、成熟和功能的调节可能与其在控制自身免疫性疾病、移植及其他免疫介导病症中的特异性免疫反应的免疫调节作用相关。
