Munroe Melissa E, Arbiser Jack L, Bishop Gail A
Department of Microbiology, University of Iowa, IA 52242, USA.
J Immunol. 2007 Jul 15;179(2):753-63. doi: 10.4049/jimmunol.179.2.753.
Honokiol (HNK), a phenolic compound isolated and purified from magnolia, has been found to have a number of pharmacologic benefits, including anti-angiogenic and anti-inflammatory properties. HNK has long been used in traditional Asian medicine without toxic side effects. We and others have extensively studied signaling to B cells by CD40 and its Epstein Barr viral mimic, latent membrane protein 1 (LMP1), which has been implicated in exacerbation of chronic autoimmune disease. We asked whether HNK could inhibit CD40 and LMP1 inflammatory signaling mechanisms. In vivo, HNK stabilized the severity of symptomatic collagen-induced arthritis in both CD40-LMP1 transgenic mice and their congenic C57BL/6 counterparts. Ex vivo studies, including collagen-specific serum Ab and Ag recall responses, as well as CD40 or LMP1-mediated activation of splenic B cells, supported the anti-inflammatory effects of HNK. In mouse B cell lines expressing the human CD40-LMP1 chimeric receptor, CD40- and LMP1-mediated NF-kappaB and AP-1 activation were abrogated in a dose-dependent manner, with a concomitant decrease in TNF-alpha and IL-6. These promising findings suggest that the nontoxic anti-inflammatory properties of HNK could be valuable for blocking the autoimmune response.
厚朴酚(HNK)是一种从木兰中分离纯化出来的酚类化合物,已被发现具有多种药理益处,包括抗血管生成和抗炎特性。厚朴酚长期用于传统亚洲医学,且无毒性副作用。我们和其他人广泛研究了CD40及其爱泼斯坦-巴尔病毒模拟物潜伏膜蛋白1(LMP1)对B细胞的信号传导,这与慢性自身免疫性疾病的加重有关。我们询问厚朴酚是否能抑制CD40和LMP1的炎症信号传导机制。在体内,厚朴酚稳定了CD40-LMP1转基因小鼠及其同基因C57BL/6对照小鼠中症状性胶原诱导性关节炎的严重程度。体外研究,包括胶原特异性血清抗体和抗原回忆反应,以及CD40或LMP1介导的脾B细胞活化,支持了厚朴酚的抗炎作用。在表达人CD40-LMP1嵌合受体的小鼠B细胞系中,CD40和LMP1介导的NF-κB和AP-1活化以剂量依赖性方式被消除,同时TNF-α和IL-6减少。这些有前景的发现表明,厚朴酚的无毒抗炎特性对于阻断自身免疫反应可能具有重要价值。