In Table 1 the total number of genes regulated in these comparisons, and genes that responded to Salmonella in the 8 hour segments find more of pig 3 were presented. In contrast to pig 2 and 4, in pig 3 a limited number of genes were found regu lated 8 hours after challenge with Salmonella, despite this pig showed a strong IL8 response similar as ob served in pig 4. Moreover, compared to pig 4, and pig 2 this pig showed a relatively faint IL1B response at 2 hours that quickly descended to a normal level within Inhibitors,Modulators,Libraries 4 hours. Also, this pig failed to produce an REG3A response at 8 hours. Nevertheless, 21 out of the 37 genes regulated in pig 3 were similar to genes regulated in pig 2 andor 4 e. g. the highly up regulated CYR61, a gene that responded to several pathogenic bacteria in epithelial cells.

This suggested that exposure to Salmonella had proceeded equally well in all three pigs, and prompted us to investigate the role of the 16 genes exclusively regulated in pig 3 at 8 hours. Using bioinformatics program STITCH2 relevant protein protein associations were detected for 19 out of the 37 genes, including associ ations Inhibitors,Modulators,Libraries of proteinsgenes with corticosteroid metabolism. Among these 19 genes was the enzyme hydroxysteroid 11 beta dehydrogenase B2, which interconverts cortisol and cortisone. Determination of cortisol in mucosal scrapings detected a significant higher level in pig 3 at 4 hours than in scrapings of pig 2 and 4, suggesting that down regulation of HSD11B2 at 8 hours in pig 3 was re lated to the metabolism of cortisol. In addition, a strong down regulation of TFF2 and RAC1 mRNA expression was observed in pig 3 at 8 hours.

TFF2 plays a role in mu cosal protection and repair in the intestine and was found up regulated at sites of ulceration in various chronic in flammatory diseases. Inhibitors,Modulators,Libraries The secreted Inhibitors,Modulators,Libraries Salmonella effector protein SopE interacts with host Rho GTPases like RAC1 in epithelial cells and macrophages and stimulates RAC1 mediated cytokine production and cytoskeletal reorga nizations, i. e. forming of membrane ruffles that facilitate invasion of these cells with Salmonella. In pig 3, down regulation of RAC1 could impair these processes and prevent or reduce the production of inflammatory cy tokines like IL1B. Sets of regulated genes in individual pigs were separ ately loaded into GeneDecks to assign genes to a spe cific pathway.

Significant immunological pathways were selected from output files and presented in Additional Inhibitors,Modulators,Libraries file 2 Table S2. The majority of pathways called for pig 2 and 4 reflected an inflammatory response induced by a bacterial infection, and were not called for pig 3. The genes of the MAPK and gluco corticoid receptor signaling directly pathways regulated in pig 3 showed little resemblance with the genes of these pathways regulated in pig 2 and 4.