dublin or L. plantarum) and early changes in gene expression were analyzed (Table 5). Table 4 Clinical parameters for patients in response to bacterial DNA experiments. Table 5 Gene expression changes (>1.5 fold) in biopsies from CD and UC patients in comparison with controls in response to bacterial DNA. Controls A total of 9 genes showed a ��1.5 fold change in response to bacterial DNA, with 2 www.selleckchem.com/products/Y-27632.html gene responses specific to L. plantarum and 4 specific to S. dublin. Gene responses similar to both bacterial DNAs included an up-regulation of lymphotoxin �� (LTA), CCR2, CD19, and CD40LG. Specific responses to L. plantarum included an up-regulation of IL10 and a down-regulation of IL4. Specific responses to S. dublin included an up-regulation of IL5, CCR7, and TNFRSF18 and a down-regulation of IL13.
Ulcerative Colitis In UC patients, a total of 20 genes showed a fold change of ��1.5 to bacterial DNA, with 7 gene responses specific to L. plantarum and 4 specific to S. dublin. Again, several gene responses were similar to both bacterial DNAs, and included a down-regulation of IL5, LTA, and an up-regulation of AGTR1 and IL1A. Specific responses to L. plantarum included a down-regulation of IL12B, CCR2, FASLG, TFRC, and an up-regulation of CXCR3, TBX21, and REN. Specific responses to S. dublin included a down-regulation of CD3E and an up-regulation of CCL19, CXCL10, and CXCL11. Crohn’s Disease In CD patients, a total of 18 genes showed a fold change of ��1.5 to bacterial DNA, with 4 gene responses specific to L. plantarum and 8 specific to S. dublin.
Responses similar to both bacterial DNAs included a down-regulation of IL13, HLADRB1, TNFRSF18, and C3, and an up-regulation of IL17 and REN. Specific responses to L. plantarum included a down-regulation of IL6 and IFN1. CD patients were generally more responsive to S. dublin compared with either controls or UC patients, with an upregulation of IL1A, IL1B, IL8, CCL3, CXCL11, and a down-regulation of CCL19 and CD19. Gene Networks of DNA-treated and Control Biopsies Alterations in gene expression in the cultured biopsies were entered into the Ingenuity Pathway Analysis (IPA) database and functional networks identified in order to provide biological context to the differentially expressed genes (Figures 3,,44,,5).5). This approach allows for changes in gene expression to be related to functional changes within cellular pathways.
Early tissue responses to S. dublin in control patients (Figure 3) were linked with chemokine and cytokine responses along with NF-��B and STAT6 signaling pathways. In contrast, Carfilzomib the response of control patients to L. plantarum (Figure 3) involved an up-regulation of IL-10 and involvement of STAT3 and STAT6 pathways, indicative of an anti-inflammatory response. This would be in agreement with our previous studies showing DNA from probiotic strains to have a differential effect on epithelial and immune responses compared with DNA from pathogenic strains [9].