A mixture of Lactobacillus sp. modulates the expression of inflammatory molecules, signalling kinases and nuclear receptors in LPS-treated Caco-2 cell culture model

Abstract

Abstract The treatment of intestinal inflammation pathologies (also known as Inflammatory Bowel Diseases, IBD) has included a large variety of strategies, from pharmaceutical to traditional medicine and dietary therapies. In the last years, numerous efforts were undertaken to demonstrate the health promoting activities of probiotics in intestinal inflammation and more other pathologic conditions. The aim of our study was to evaluate the effects of a probiotic mixture of Lactobacillus sp. on the inflammatory mediators and signalling pathways as well as nuclear receptors in colonic Caco-2 cells. Human adenocarcinoma Caco-2 cells were challenged in vitro with lipopolysaccharide (LPS) for 4 hours for the induction of inflammation. The LPS-treated cells were cultured for additional 24 hours in the presence of Lactobacillus (Lb) mixture (3 x108 CFU/mL total Lb). Genomic and proteomic array approaches were used to analyse the profile expression of 18 key genes and their proteins involved in intestinal inflammatory response (chemokines, adhesion molecules, growth factors and matrix metalloproteinases inhibitors) as well as signalling markers (Akt, GSK) and nuclear receptors (NF-kB/RELA, Nrf2, AhR). Our study demonstrated that the probiotic Lactobacillus mixture could decrease LPS-induced inflammatory mediator expressions (chemokines, growth factors and matrix metalloproteinases inhibitor) at gene and protein level. This down-regulation exerted by Lb. mix in LPS-treated Caco-2 cells seemed to be regulated through inhibition of both the PI3K/AKT and NF-κB signalling pathways. Additionally, AhR activation induced by LPS was reduced by probiotic mixture under the level of LPS-treated cells. These beneficial effects of Lactobacillus mixture support their use as inflammatory modulators in intestinal disorders.