Department of Rehabilitation Medicine of Korean Medicine, Dongguk University Ilsan Hospital, Goyang, Gyeonggi, Republic of Korea.
Biofactors. 2019 Mar;45(2):223-235. doi: 10.1002/biof.1475. Epub 2018 Dec 11.
Intestinal epithelial cells (IECs) respond to intruders and their cellular molecules by displaying inflammatory state that can be abrogated by probiotics. However, the molecular mechanisms underlying the beneficial activity of probiotic strains have yet to be elucidated. This study was conducted to investigate whether probiotic strains have immunoregulatory effects in IECs, and how they respond to bacterial lipopolysaccharide (LPS) in vitro. Caco2 cells were stimulated with LABs and followed by LPS. The expression of different cytokines that involved in toll-like receptor (TLR) signaling was analyzed. Caco2 cells that were exposed to LPS showed upregulated expression of IL-6, CXCL8, CCL2, and BPI that were counteracted by LAB strains through the modulation of TLR negative regulators (A20, Tollip, SIGIRR, and IRAKM), p38 MAPK and p65 NF-κB signaling. Lactobacillus plantarum, L. farciminis, and L. pentosus unveiled better activity as compared to other strains. Moreover, LAB strains were the potent inducers of immunoregulatory cytokines in coculture system. The expression of IL-10 and TGF-β were found to be higher as compared with LPS. Conversely, TNF-α at the protein level was dampened by LAB strains in both the apical and basolateral compartments. Collectively, our results demonstrated that the selected LAB strains exert profound immunoregulatory effects in response to LPS on IECs; however, further studies in vivo and in clinical settings are important to corroborate these effects. © 2018 BioFactors, 45(2):223-235, 2019.
肠上皮细胞 (IECs) 通过显示炎症状态来响应入侵者及其细胞分子,而益生菌可以消除这种炎症状态。然而,益生菌菌株的有益活性的分子机制尚未阐明。本研究旨在研究益生菌菌株是否对 IEC 具有免疫调节作用,以及它们如何在体外响应细菌脂多糖 (LPS)。用 LABs 刺激 Caco2 细胞,然后用 LPS 处理。分析了涉及 Toll 样受体 (TLR) 信号的不同细胞因子的表达。用 LPS 处理的 Caco2 细胞表现出 IL-6、CXCL8、CCL2 和 BPI 的表达上调,而 LAB 菌株通过调节 TLR 负调节剂 (A20、Tollip、SIGIRR 和 IRAKM)、p38 MAPK 和 p65 NF-κB 信号来拮抗这些上调。与其他菌株相比,植物乳杆菌、L. farciminis 和 L. pentosus 表现出更好的活性。此外,LAB 菌株在共培养系统中是免疫调节细胞因子的有效诱导剂。与 LPS 相比,发现 IL-10 和 TGF-β 的表达更高。相反,LAB 菌株在顶端和基底外侧隔室均下调了 TNF-α 的蛋白水平。总之,我们的研究结果表明,所选的 LAB 菌株在 IEC 对 LPS 的反应中发挥了深刻的免疫调节作用;然而,在体内和临床环境中进行进一步的研究对于证实这些作用很重要。