Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.
Cytokine. 2019 Sep;121:154718. doi: 10.1016/j.cyto.2019.05.005. Epub 2019 May 29.
A single layer of epithelial cells creates an interface between the host and microorganisms colonizing the gastrointestinal tract. In a healthy intestine, commensal bacteria and their metabolites can interact with epithelial cells as they are identified by Toll-like receptors (TLRs); This interaction results in homeostasis and immune responses. The present study aimed at evaluating Faecalibacterium prausnitzii- and extracellular vesicles (EVs)-induced expression of involved genes in TLRs signaling pathway and cytokines production in Caco-2 cell line. In this study, Caco-2 cell line was treated with F. prausitzii and its EVs. Using the protein levels of 12 cytokines were also evaluated by ELISA assay. F. prausnitzii induced upregulation in FOS, JUN, TNF-α, NFKB1, TLR3, IKBKB and CD86 genes. Furthermore, stimulation of Caco-2 cells with EVs derived from F. prausnitzii induced upregulation of CXCL8, CCL2, FOS, MAP2K4, TLR7, TLR3, IRF1, NFKBIA and TNF-α genes. Based on ELISA assay, Caco-2 cells treated with F. prausnitzii and its EVs showed a significant increase in TNF-α, IL-4, IL-8, and IL-10 expression and significant decreased in IL-1, IL-2, IL-6, IL-12, IL-17a, IFN-γ compared to the control group (P < 0.05). In conclusion, EVs derived from F. prausnitzii showed greater efficacy in decreasing the inflammatory cytokines and increasing the anti-inflammatory cytokines, compared to F. prausnitzii. Our findings can be used as a theoretical model for EVs application in the potential treatment of inflammation.
单层上皮细胞在宿主和定植于胃肠道的微生物之间形成界面。在健康的肠道中,共生细菌及其代谢物可以与上皮细胞相互作用,因为它们被 Toll 样受体 (TLR)识别;这种相互作用导致了体内平衡和免疫反应。本研究旨在评估普氏粪杆菌及其细胞外囊泡 (EVs) 诱导 TLRs 信号通路相关基因表达和细胞因子产生的作用在 Caco-2 细胞系中的作用。在这项研究中,用 F. prausitzii 和其 EVs 处理 Caco-2 细胞系。还通过 ELISA 测定评估了 12 种细胞因子的蛋白水平。F. prausnitzii 诱导 FOS、JUN、TNF-α、NFKB1、TLR3、IKBKB 和 CD86 基因上调。此外,用源自 F. prausnitzii 的 EVs 刺激 Caco-2 细胞,诱导 CXCL8、CCL2、FOS、MAP2K4、TLR7、TLR3、IRF1、NFKBIA 和 TNF-α基因上调。基于 ELISA 测定,用 F. prausnitzii 和其 EVs 处理的 Caco-2 细胞显示 TNF-α、IL-4、IL-8 和 IL-10 的表达显著增加,而 IL-1、IL-2、IL-6、IL-12、IL-17a 和 IFN-γ的表达显著降低与对照组相比(P<0.05)。总之,与 F. prausnitzii 相比,源自 F. prausnitzii 的 EVs 在降低炎症细胞因子和增加抗炎细胞因子方面显示出更大的疗效。我们的研究结果可以作为 EVs 应用于炎症潜在治疗的理论模型。