In the periodontitis-affected tissues showed regulated pathways indicative of inflammation, such as cytokine signaling, chemokine signaling and the JAK-STAT signaling pathway. Several cytokines such as interleukins, which are involved in periodontits, signal through the JAK-STAT signaling pathway. On the other hand, in the healthy biopsies, pathways were indicative of non-inflammatory processes that may be involved in the maintenance of the healthy gingival tissue. Future studies should also include investigation of genes within these pathways, which may contribute to understanding, prevention and treatment of periodontitis. Differential gene expression LY2835219 CDK inhibitor analyses of periodontitis-affected vs. healthy gingival tissues showed the majority of differentially expressed genes to be upregulated in the periodontitis-affected tissues. Furthermore, GO enrichment analysis among these differentially expressed genes demonstrated that most of these genes were involved in immune and inflammatory processes. This is in line with the increased inflammatory response in the tissue, and also in accordance with our previous microarray studies on inflammatory-stimulated cell cultures reporting that gene expression profiles of TNFa-stimulated cells show an induction of inflammatory genes. Up to date, RNA-Seq studies aimed to identify new genes involved in the pathogenesis of periodontits have not been reported.The activation of the transcription factor NF-kB leads to a wide range of cellular responses including proliferation, apoptosis, and angiogenesis. More than 500 genes have been reported to be expressed upon activation of NF-kB including the immuneresponsive and NF-kB regulatory genes in addition to proliferation-, invasion/metastasis- and angiogenesis-promoting genes. While NF-kB activation in normal cells is mostly transient, it is constitutively activated in malignant tumors and stimulates the growth of malignant cells. Thus, the control of NF-kB activity is critical in cancer therapies. NF-kB is activated through two main pathways known as the classical and the non-classical pathways. In the classical pathway, NF-kB is activated by TNFa, IL1b, or bacterial products. IL-1 stimulation results in the formation of a signaling complex composed of TRAF6, TAK1, and MEKK3 which leads to the activation of TAK1 and MEKK3. IKK complex, which is a heterotrimer of IKKa, IKKb, and NEMO in the classical pathway, is recruited to the complex, and NEMO is ubiquitinated leading to the activation of IKK. Activated IKK then phosphorylates IkBa in the NF-kB complex, which is a heterotrimer of IkBa, p50, and p65. The phosphorylated IkBa is subsequently ubiquitinated and subjects to proteasomal degradation leading to the release of inhibition on NF-kB by IkBa. Thus activated NF-kB translocates to the nucleus, where it binds to the promoter or enhancer region of target genes. Interestingly, the concentration of nuclear NF-kB is known to oscillate by the application of TNFa. The analysis of a population of cells showed damped oscillation of nuclear NF-kB with a period of 1.5–3 hrs. Damped oscillation of NF-kB was also reported in a single cell analysis with a period of 1–2 hrs using RelA fused to red fluorescent protein. It has been reported that changes in the oscillation pattern of nuclear NF-kB led to changes in the gene expression pattern. Hoffmann et al. reported that shorter and longer applications of TNFa resulted respectively and this difference led to the expression of quick and slow responsive genes.