Research Institute of Modern Biological Techniques, University of Zanjan, 45371-38791 Zanjan, Iran.
Department of Food Science and Engineering, Faculty of Agriculture, University of Zanjan, 45371-38791 Zanjan, Iran.
Int J Biol Macromol. 2020 Dec 15;165(Pt A):619-624. doi: 10.1016/j.ijbiomac.2020.09.219. Epub 2020 Sep 30.
Kefiran is a water-soluble polysaccharide well recognized as a bioactive ingredient to enhance nutritional and health-promoting features. Also, some therapeutic properties have made this macromolecule an active ingredient in ointments and oral anti-inflammatory drugs. However, the details of the molecular and cellular aspects of these effects have not been addressed. In this study, lipopolysaccharides (LPS)-induced monocytes, lymphocytes, and monocyte-derived dendritic cells (MDDCs) as representative cells for both innate and adaptive immunity were treated with kefiran for 2 h. Kefiran had an anti-inflammatory effect on monocytes to reduce pro-inflammatory cytokines, interleukin 1 β (IL-1β) & tumor necrosis factor α (TNF-α), as well as nuclear factor kappa b (NF-kb). However, it did not affect lymphocytes. Overexpression of Toll-like receptor 4 (TLR4) in LPS-induced cells was not reduced after kefiran treatment. Kefiran balanced MDDCs secretion of pro/anti-inflammatory cytokines by reducing and enhancing the expression of IL-1β and interleukin 10 (IL-10), respectively. Also, kefiran decreased the number of apoptotic immature MDDCs and promoted dose-dependent phagocytosis capacity of MDDCs. According to the results of the current study, it may be concluded that the immunomodulatory effects of kefiran are due to antagonist against innate immune receptors especially TLR4. The results of this study can be used as a guide to developing kefiran-based non-aggressive anti-inflammatory drugs. Furthermore, understanding the immunobiological effects of kefiran on monocytes and lymphocytes was another outcome of this study.
凯菲兰是一种水溶性多糖，被公认为具有增强营养和促进健康的生物活性成分。此外，一些治疗特性使这种大分子成为软膏和口服抗炎药物的有效成分。然而，这些作用的分子和细胞方面的细节尚未得到解决。在这项研究中，用脂多糖（LPS）诱导的单核细胞、淋巴细胞和单核细胞衍生的树突状细胞（MDDC）作为固有和适应性免疫的代表性细胞，用凯菲兰处理 2 小时。凯菲兰对单核细胞具有抗炎作用，可减少促炎细胞因子白细胞介素 1β（IL-1β）和肿瘤坏死因子α（TNF-α）以及核因子 kappa b（NF-kb）。然而，它对淋巴细胞没有影响。用 LPS 诱导的细胞中转染 Toll 样受体 4（TLR4）后，凯菲兰处理并不能降低 TLR4 的表达。凯菲兰通过降低和增强白细胞介素 1β（IL-1β）和白细胞介素 10（IL-10）的表达，平衡 MDDC 分泌促炎/抗炎细胞因子。此外，凯菲兰还减少了凋亡未成熟 MDDC 的数量，并促进了 MDDC 的吞噬能力，呈剂量依赖性。根据本研究的结果，可以得出结论，凯菲兰的免疫调节作用是由于其作为先天免疫受体（特别是 TLR4）拮抗剂的作用。本研究的结果可作为开发基于凯菲兰的非侵袭性抗炎药物的指导。此外，了解凯菲兰对单核细胞和淋巴细胞的免疫生物学作用是本研究的另一个结果。
