Kiššová Zuzana, Tkáčiková Ľudmila, Mudroňová Dagmar, Bhide Mangesh R
Institute of Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia.
Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia.
Life (Basel). 2022 Nov 22;12(12):1955. doi: 10.3390/life12121955.
The gastrointestinal tract is the largest and most complex component of the immune system. Each component influences the production and regulation of cytokines secreted by intestinal epithelial cells. The aim of this study was to see how the probiotic strain L26 and its exopolysaccharide (EPS) affect porcine intestinal-epithelial cells IPEC-J2 infected with Typhimurium. The results revealed that infection up-regulated all studied pro-inflammatory cytokines such as TNF-α, IL-8, IL-6 and TLR4, TLR5 signaling pathways, while decreasing the expression of TGF-β. An immunosuppressive activity was found in EPS-treated wells, since the transcriptional levels of the studied pro-inflammatory cytokines were not increased, and the pretreatment with EPS was even able to attenuate up-regulated pro-inflammatory genes induced by infection. However, there was a significant increase in the expression of mRNA levels of IL-8 and TNF-α in L26-treated cells, although this up-regulation was suppressed in the case of pretreatment. The immunoregulatory function of was also confirmed by the increased level of mRNA expression for TGF-β, a known immunosuppressive mediator. The most relevant finding of this ex vivo study was a case of immunity modulation, where the probiotic strain stimulated the innate immune-cell response which displayed both anti- and pro-inflammatory activities, and modulated the expression of TLRs in the IPEC-J2 cell line. Our findings also revealed that the pretreatment of cells with either EPS or live lactobacilli prior to infection has a suppressive effect on the inflammatory response induced by Typhimurium.
胃肠道是免疫系统最大且最复杂的组成部分。每个组成部分都会影响肠道上皮细胞分泌的细胞因子的产生和调节。本研究的目的是观察益生菌菌株L26及其胞外多糖（EPS）如何影响感染鼠伤寒沙门氏菌的猪肠道上皮细胞IPEC-J2。结果显示，感染上调了所有研究的促炎细胞因子，如TNF-α、IL-8、IL-6以及TLR4、TLR5信号通路，同时降低了TGF-β的表达。在EPS处理的孔中发现了免疫抑制活性，因为所研究的促炎细胞因子的转录水平没有增加，并且用EPS预处理甚至能够减弱由感染诱导的促炎基因的上调。然而，在L26处理的细胞中，IL-8和TNF-α的mRNA水平表达显著增加，尽管这种上调在预处理的情况下受到抑制。TGF-β（一种已知的免疫抑制介质）的mRNA表达水平升高也证实了其免疫调节功能。这项体外研究最相关的发现是一个免疫调节的案例，即益生菌菌株刺激了具有抗炎和促炎活性的先天免疫细胞反应，并调节了IPEC-J2细胞系中TLR的表达。我们的研究结果还表明，在感染前用EPS或活的乳酸杆菌对细胞进行预处理，对鼠伤寒沙门氏菌诱导的炎症反应具有抑制作用。
