Liu Qiuyan, Shu Xiaoli, Sun Anna, Sun Qiaoling, Zhang Chaoxiong, An Huazhang, Liu Jikai, Cao Xuetao
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, PR China.
Int Immunopharmacol. 2008 Aug;8(8):1103-11. doi: 10.1016/j.intimp.2008.04.001. Epub 2008 Apr 30.
Dendritic cells (DCs) play crucial roles in linking innate immunity and adaptive immunity, thus being regarded as one of the important targets of immunosuppressant. Natural small molecule products isolated from plants, such as fungal metabolites, have been shown to be effective in the treatment of cancer, inflammation and autoimmune diseases. Albaconol is a new kind of prenylated resorcinols isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens, and has been shown to inhibit tumor cell growth. Considering that most of small molecule compounds with antitumor activity always exert immunosuppressive effect, so we wonder whether albaconol could inhibit maturation and antigen presentation of DCs, thus acting as immunosuppressant. Here we demonstrate that albaconol significantly inhibits LPS-induced production of proinflammatory cytokines TNF-alpha, IL-6, IL-1beta, and expression of MHC-II and co-stimulatory molecules by DCs. Furthermore, albaconol markedly inhibits T cell-stimulating capacity of DCs and DCs-initiated antigen-specific T cell response, indicating albaconol can inhibit phenotypic and functional maturation of DCs. Inhibition of LPS-induced NF-kappaB activation may contribute to the above immunosuppressive or anti-inflammatory activities of albaconol. Therefore, our results suggest that natural small molecule albaconol may be a potential immunosuppressive and anti-inflammatory agent through suppressing DCs function via impairment of NF-kappaB activation.
树突状细胞(DCs)在连接固有免疫和适应性免疫方面发挥着关键作用,因此被视为免疫抑制剂的重要靶点之一。从植物中分离出的天然小分子产物,如真菌代谢产物,已被证明在治疗癌症、炎症和自身免疫性疾病方面有效。阿尔巴康醇是一种从不可食用的蘑菇融合白桩菇子实体中分离出的新型异戊烯基间苯二酚,已被证明能抑制肿瘤细胞生长。鉴于大多数具有抗肿瘤活性的小分子化合物总是发挥免疫抑制作用,所以我们想知道阿尔巴康醇是否能抑制DCs的成熟和抗原呈递,从而起到免疫抑制剂的作用。在此我们证明,阿尔巴康醇能显著抑制脂多糖(LPS)诱导的DCs促炎细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)的产生,以及主要组织相容性复合体II类分子(MHC-II)和共刺激分子的表达。此外,阿尔巴康醇显著抑制DCs刺激T细胞的能力以及DCs启动的抗原特异性T细胞反应,表明阿尔巴康醇能抑制DCs的表型和功能成熟。抑制LPS诱导的核因子-κB(NF-κB)激活可能有助于阿尔巴康醇的上述免疫抑制或抗炎活性。因此,我们的结果表明,天然小分子阿尔巴康醇可能是一种潜在的免疫抑制和抗炎剂,它通过损害NF-κB激活来抑制DCs功能。