Studies on effectiveness of the Chinese medicine against intractable mycobacterial infection

本文研究了多种中药等免疫调节剂对鸡分枝杆菌复合群（MAC）感染的增强作用。获得了以下结果。(1)MBST能增强巨噬细胞（Mφ）抗MAC活性。而除麻圭郁坎藤对宿主Mφ的抗MAC活性有较弱的增强作用外，其余45种中药均未表现出明显的抗MAC活性。因此，似乎在大多数中药的情况下，通过直接增强Mφ和/或淋巴细胞功能来增加Mφ抗细胞内MAC的抗微生物活性的功效通常较弱。(2)MBST对除Kakkon-To外的各型Mφ产生活性氧中间产物（ROI）的诱导作用均较弱。(3)这些作用仅在用中药预处理的塑料威尔斯孔中发现。因此有 ...更多信息 可能MBST激活的Mφ的信号转导模式存在显著差异，这取决于细胞-基质粘附的强度。(4)ATP可增强Mφ的抗MAC活性，但与MBST联合处理Mφ并不能显著增加Mφ产生活性氮中间产物。(5)伴刀豆球蛋白A（ConA）诱导的T细胞有丝分裂反应被Ouren-Gedoku-To和Hochu-Ekki-To显著抑制，而MBST的抑制效果弱于它们。而其它17种中药对T细胞ConA有丝分裂无明显影响。(6)作为开发利用siRNA调控各种Mφ功能的体外实验系统的第一步，我们检测了是否可以通过使用PD-L特异性的反义寡核苷酸来控制Mφ抑制剂活性。PDL特异性反义寡核苷酸有降低Mφ抑制活性的趋势。(7)本论文重点研究了吡啶甲酸（PA）作为一种天然有机产物，作为一种比传统中药更好的免疫调节剂。我们发现PA增强了Mφ对细胞内MAC的抗菌活性。此外，PA诱导THP-1 Mφ的早期凋亡事件，而不诱导DNA断裂特征性的中晚期凋亡。少

We examined the effects of immunomodulating agents including various Chinese traditional medicines in potentiating of the host antimicrobial functions against Mycobacterium avium complex (MAC) infection. The following findings were obtained. (1) Mao-Bushi-Saishin-To (MBST) enhanced the macrophage (Mφ) anti-MAC activity. However, forty-five other Chinese traditional medicines did not exhibit such significant effects except for weak effect by Ma-Kyou-Yoku-Kan-To in potentiating anti-MAC activity of host Mφs. Thus, it appears that the efficacy in increasing of the Mφ antimicrobial activity against intracellular MAC by directly augmenting Mφ and/or lymphocyte functions is generally weak in case of most Chinese medicines. (2) The production of reactive oxygen intermediate (ROI) by various types of Mφs were weak induced by MBST treatment except for Kakkon-To. (3) These effects were found only when Mφs were pre-treated with test Chinese traditional medicine in plastic wells. Therefore, it is … More likely that there are significant differences in the mode of signal transduction in MBST-activated Mφs which depend on intensity of cell-matrix adhesion. (4) Treatment of Mφs with ATP, which potentiate Mφ anti-MAC activity, in combination with MBST did not significantly increase the production of reactive nitrogen intermediate by Mφs. (5) Concanavalin A (Con A)-induced T cell mitogenic responses were significantly inhibited by Ouren-Gedoku-To and Hochu-Ekki-To, while inhibitory efficacy of MBST was weaker than them. On the other hand, other 17 Chinese traditional medicines did not exhibit such effect on T cell Con A mitogenesis. (6) As the first step in the development of in vitro experimental systems to regulate various Mφ functions by using siRNA, we examined whether Mφ suppressor activity could be controlled by using antisense oligonucleotides specific to PD-L. There was observed the tendency that Mφ suppressor activity was decreased to some extent by the PDL-specific antisense oligonucleotides. (7) We focused on picolinic acid (PA), a natural organic product, as an immunomodulator better than Chinese traditional medicines. We found that PA potentiated Mφ antimicrobial activity against intracellular MAC. In addition, PA induced the early phase apoptotic events in THP-1 Mφs, without inducing DNA fragmentation characteristic to the middle to late phase apoptosis. Less