jejuni BCE. The dominant component of this response concerned up regulation of chemokines that would act to induce the influx of acute inflammatory cells that characterize Campylobacter colitis. Our data are remarkably similar to transcriptomic

Dactolisib datasheet data reported by Hinata et al., who activated NF-κB by transfecting clones expressing subunits of NF-κB to show up-regulation of the chemokines CXCL3 (GRO3) IL8, CXCL6, CXCL2 (GRO2), CXCL20 (SCYA20), CXCL1 (GRO1), CCL2 (CXYA2) as well as IL1α and CSF2, all of which were also significantly up-regulated in our study [19]. The NFKB1, NFKB2 and RELB components of NF-κB are also similarly up-regulated in our study. Other changes that are likely to be of functional importance and are the up-regulation of COX2 (PTGS2), TNIP2, MYC, SOD2, ELF3 and ICAM1 (Additional file 1), where all of these processes are also downstream targets of NF-κB [20] and mediators

of feedback inhibition of NF-κB activation such as NFKBIA (IκB) [9], TNIP1 [21] and TNIP2 (Figure 3) [22]. A central role for NF-κB is also supported by data using the monocytic cell line THP-1 [23]. Studies in which Caco-2 cells were incubated with live bacteria ROCK inhibitor resulted in expression of many genes similar to those reported here, including chemokines, but additionally, the NF-κB inhibitor NFKBIZ [24]. This difference may reflect the ability of live bacteria to invade cells and/or elaborate a CLDT with DNase activity [6]. The pattern of significantly down-regulated genes (Table 3) is remarkably different with a reduction in expression in constitutively expressed genes concerned with nucleotide Cell Cycle inhibitor synthesis, transcription, DNA replication, mitosis, structural protein synthesis, membrane transport and energy metabolism. These changes likely reflect the reprioritization of cellular metabolism in response to pro-inflammatory products. Whether the changes caused by the C. jejuni BCE would lead to increased or reduced apoptosis is difficult to predict, especially as HCA-7 lack a functional TP53 protein, although these cells are capable of apoptosis given the appropriate signal [25]. Invasive C. jejuni infection can cause cell

death in HCA-7 cells [16], although we did not see this with the addition of BCE [8]. Increased expression of members of the death receptor pathway, the TNFα superfamily and their receptors, but also of TNFα agonists may imply regulated stiripentol activation of pro-apoptotic activity [26–30]. Up-regulation of TRAIL, DR5, and FAS ligand acting via FADD, the universal adaptor protein known domain-containing members of the TNF receptor superfamily, would successively activate caspases 8, 10 and 3 as well as possible G1-S cell cycle progression [27]. However, the antagonists TNFAIP3, FLIP and cIAP, which respectively inhibit apoptosis via TRAF6, caspases 8, 9, 10 and TRAF-2 directly or indirectly are also prominent amongst the up-regulated genes [29–32]. Moreover, several other key proteins for the cell cycle and apoptosis are affected.