Hrdý Jiří, Súkeníková Lenka, Petrásková Petra, Novotná Olga, Kahoun David, Petříček Miroslav, Chroňáková Alica, Petříčková Kateřina
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, 116 36 Prague, Czech Republic.
Faculty of Science, University of South Bohemia, 370 05 České Budějovice, Czech Republic.
Microorganisms. 2020 Apr 25;8(5):621. doi: 10.3390/microorganisms8050621.
Current treatment of chronic diseases includes, among others, application of cytokines, monoclonal antibodies, cellular therapies, and immunostimulants. As all the underlying mechanisms of a particular diseases are not always fully clarified, treatment can be inefficient and associated with various, sometimes serious, side effects. Small secondary metabolites produced by various microbes represent an attractive alternative as future anti-inflammatory drug leads. Compared to current drugs, they are cheaper, can often be administered orally, but still can keep a high target-specificity. Some compounds produced by actinomycetes or fungi have already been used as immunomodulators-tacrolimus, sirolimus, and cyclosporine. This work documents strong anti-inflammatory features of another secondary metabolite of streptomycetes-manumycin-type polyketides. We compared the effect of four related compounds: manumycin A, manumycin B, asukamycin, and colabomycin E on activation and survival of human monocyte/macrophage cell line THP-1. The anti-cancer effect of manucycine A has been demonstrated; the immunomodulatory capacities of manumycin A are obvious when using micromolar concentrations. The application of all four compounds in 0.25-5 μM concentrations leads to efficient, concentration-dependent inhibition of IL-1β and TNF expression in THP-1 upon LPS stimulation, while the three latter compounds show a significantly lower pro-apoptotic effect than manumycin A. We have demonstrated the anti-inflammatory capacity of selected manumycin-type polyketides.
慢性病的当前治疗方法包括，除其他外，应用细胞因子、单克隆抗体、细胞疗法和免疫刺激剂。由于特定疾病的所有潜在机制并不总是完全清楚，治疗可能效率低下，并伴有各种有时严重的副作用。各种微生物产生的小次生代谢产物作为未来抗炎药物先导物是一种有吸引力的替代选择。与目前的药物相比，它们更便宜，通常可以口服，但仍能保持高靶向特异性。放线菌或真菌产生的一些化合物已被用作免疫调节剂——他克莫司、西罗莫司和环孢素。这项工作记录了链霉菌的另一种次生代谢产物——马努霉素型聚酮化合物的强大抗炎特性。我们比较了四种相关化合物：马努霉素A、马努霉素B、明日霉素和colabomycin E对人单核细胞/巨噬细胞系THP-1激活和存活的影响。马努辛A的抗癌作用已得到证实；当使用微摩尔浓度时，马努霉素A的免疫调节能力很明显。在0.25 - 5μM浓度下应用所有四种化合物可有效、浓度依赖性地抑制LPS刺激后THP-1中IL-1β和TNF的表达，而后三种化合物的促凋亡作用明显低于马努霉素A。我们已经证明了所选马努霉素型聚酮化合物的抗炎能力。
